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TW202224701A - 包含免疫刺激性及抗原性多肽的酵母菌疫苗載體以及其使用方法 - Google Patents

包含免疫刺激性及抗原性多肽的酵母菌疫苗載體以及其使用方法 Download PDF

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TW202224701A
TW202224701A TW111105339A TW111105339A TW202224701A TW 202224701 A TW202224701 A TW 202224701A TW 111105339 A TW111105339 A TW 111105339A TW 111105339 A TW111105339 A TW 111105339A TW 202224701 A TW202224701 A TW 202224701A
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奧莉維亞 Ｂ 福克納
麗莎 貝爾琪
李奧娜 妮可 考亨
路克 柏格曼
比利 哈吉斯
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阿肯色州大學董事會
美國德州Ａ＆Ｍ大學系統中心
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Abstract

本發明提供一種疫苗組合物，其包含含有免疫刺激性多肽與任選的抗原性多肽的酵母菌。免疫刺激性多肽與抗原性多肽表達或顯示於酵母菌疫苗組合物的表面上。本發明亦提供一種使用疫苗組合物接種於受試者的方法。

Description

包含免疫刺激性及抗原性多肽的酵母菌疫苗載體以及其使用方法
相關申請案之互相參照
本申請主張2016年5月3日提交之美國臨時專利申請號No.62/331044之優先權，全部內容於此併入作為參考。
疫苗用於起始對抗原的適應性免疫反應，特別是來自病原體的抗原，以改善或預防疾病。失活或減毒的微生物疫苗通常有效地刺激全面防護的有力的免疫反應，但是在某些情況中，這些疫苗不具防護性或僅具部份地防護性，且必須採用其他策略以開發防護性疫苗。基於微生物的疫苗不能藉由糖苷化後轉譯修飾蛋白質，以正確地表達像是病毒蛋白質的大的抗原蛋白，因此，需要發展可以糖苷化並產生安全且有效地刺激持久保護免疫反應的正確摺疊的大的抗原蛋白的酵母菌疫苗載體。
本文提供酵母菌疫苗載體。疫苗載體適合口服施用並產生對抗原快速且持久的免疫反應，且防止標的微生物的後續感染。特別地，產生的免疫反應係為一種適用於防止黏膜感染的IgA反應。
在一態樣中，提供一種酵母菌疫苗組合物。組合物包含含有編碼選自HMGB1多肽或CD40配位體的免疫刺激性多肽的免疫刺激性多核苷酸之酵母菌。酵母菌被工程化以表達HMGB1多肽或CD40配位體於酵母菌的表面上。組合物也可包含可適當地表達在酵母菌的表面上的抗原性多肽。組合物可與藥學上可接受的載體及/或佐劑組合以產生醫藥組合物。組合物可包含多於一種的抗原性多肽且多於一種的抗原性多肽可衍生自相同或是不同生物體或物種。
在另一態樣中，增強受試者的免疫反應的方法，其藉由對受試者以有效的劑量施用本文所提供的疫苗組合物與醫藥組合物，以增強受試者對於疫苗組合物與關於抗原性多肽的傳染性因子的免疫反應。
本發明提供一種能誘發對疫苗組合物或因疫苗組合物所表現的抗原性多肽的免疫反應的疫苗組合物。特別地，疫苗組合物包含工程化以於其表面上表達免疫刺激性多肽的酵母菌。酵母菌也可被工程化以於酵母菌的表面上表達額外的抗原性多肽。在特定實施例中，提供一種巴斯德畢赤酵母菌疫苗載體。疫苗載體包含編碼顯示或表達於酵母菌的表面上的免疫刺激性多肽的免疫刺激性多核苷酸序列。免疫刺激性多肽可為高遷移率族蛋白1(HMGB1)免疫刺激性多肽，或者例如CD154多肽或其片段的CD40配位體或例如CD40激動性抗體(agonistic antibody)的其他CD40致效劑。免疫刺激性多肽可使用所屬技術領域中具有通常知識者可獲得的任何方法而被表達於例如巴斯德畢赤酵母菌的酵母菌的表面上。在實例中，免疫刺激性多肽係透過由啤酒酵母菌α凝集素的3’端編碼的多醣磷脂肌醇(GPI)錨定機制錨定於酵母菌的表面上。所屬技術領域中具有通常知識者將容易理解的是，其他表達系統可被用於獲得包含於酵母菌內的免疫刺激性及/或抗原性多肽的表面表達，以產生疫苗組合物。
HMGB1蛋白被首先被辨識為對DNA結構與穩定性至關重要的DNA結合蛋白。它是一種結合DNA而沒有序列特異性的常見表達核蛋白。該蛋白質為高度保留性且在範圍從植物到哺乳動物的生物體內發現。提供雞、斑馬魚、人類、小鼠、大鼠、食蟹獼猴(crab-eating macaca)、牛、馬、犬、豬、兔子、紅鼓魚(red drum)、鯰魚(catfish)、紅笛鯛(humphead snapper)、金魚(goldfish)、眼鏡王蛇(king cobra)、豐年蝦(brine shrimp)與其他HMGB1胺基酸序列。參見SEQ ID NO：2-30與94-105。整體哺乳動物中的序列為高度保留，其具有95%胺基酸一致性且胺基酸的變化為保留式(conservative)。因此，來自一種物種的HMGB1蛋白可在功能上取代來自另一個物種的HMGB1蛋白。全長HMGB1蛋白或其部分可用作在本發明所述的疫苗載體中的HMGB1多肽。HMGB1具有稱為A1與A2及B1與B2的兩個DNA結合區域。參見Andersson and Tracey, Annu. Rev. Immunol. 2011, 29:139-162。
HMGB1係炎症介質且作為像是從壞死細胞來的核損傷的信號。於需要蛋白質的乙醯化、穿過細胞核的移位且分泌的過程中，HMGB1也可藉由單核細胞/巨噬細胞譜系的細胞而積極地分泌。胞外HMGB1藉著經由晚期糖基化最終產物(Advanced Glycated End-products，RAGE)的受體與經由Toll樣受體族(Toll-like Receptor family，TLR)，特別是TLR4的細胞膜的信號傳導作為炎症的有效介質。RAGE結合活性已被辨識且需要HMGB1 RAGE結合域的多肽。TLR4結合需要於HMGB1的B盒區域發現的雞HMGB1序列(SEQ ID NO：2)的位置106的半胱胺酸。
適當地，疫苗載體包含編碼包含雞HMGB1多肽的胺基酸150-183與89-109或其同源物的多肽的多核苷酸。參見SEQ ID NO：2。在一實例中，使用HMGB1的190胺基酸多肽。適當地，多核苷酸編碼來自與將使用疫苗組合物的受試者的相同物種的HMGB1多肽。因為HMGB1透過如上所述的大量物種係高度保留，因此HMGB1多肽與受試者(亦即：雞疫苗中使用人類HMGB1多肽)的異種組合可使用於本發明的方法。HMGB1多肽可用於增強於受試者對於在酵母菌疫苗組合物內或上呈現的外來抗原或抗原性多肽的免疫反應。所屬技術領域中具有通常知識者將理解的是，HMGB1多肽可用於增強對於在酵母菌疫苗組合物呈現的一種以上抗原性多肽的免疫反應。來自HMGB1的多肽藉由活化樹突細胞與巨噬細胞刺激至少一部份的免疫反應，從而刺激像是IL-1、IL-6、IFN-γ與TNF-α的細胞介素的產生。在一實例中，HMGB1的多肽被表現於疫苗組合物的表面上。
HMGB1的炎症活性不需要全長蛋白與已辨識的功能性片段。B盒顯示足以介導HMGB1的促發炎效應(pro-inflammatory effects)，因此HMGB1盒b1與HMGB盒b2係於本發明的上下文內的HMGB1多肽或其功能性片段。參見，例如SEQ ID NO：35與36。此外，RAGE結合位與促發炎細胞介素活性已被標定。分別地參見SEQ ID NO：37與38。因此，這些多肽係本發明的上下文內的HMGB1多肽的功能性片段。參見 SEQ ID NO：31至38。
所屬技術領域中具有通常知識者可使用像是此些於國際公開號No. WO2002092004內的方法辨識可能刺激促發炎細胞介素活性的HMGB1多肽及其片段，其全部內容於此併入本文作為參考。適當地，HMGB1多肽包含在雞HMGB1序列(HMGB RAGE 結合域或其同源物)的胺基酸150-183的RAGE結合域與介於雞HMGB1序列(SEQ ID NO：2；HMGB1 促發炎細胞介素活性或其同源物)的胺基酸89-109之間的促發炎細胞介素活性域。特別地，HMGB1多肽與功能性片段或其同源物包含分別與雞HMGB1序列的HMGB1多肽或HMGB1 盒a1、HMGB1 盒a2、HMGB1 盒b1、HMGB1 盒b2、HMGB1 RAGE結合域或HMGB1 促發炎細胞介素活性相同或至少99%相同、至少98%相同、至少95%相同、至少90%相同、至少85%相同或至少80%相同的多肽。
免疫刺激性多肽也可為CD40配位體或CD40致效劑。可於受試者中鍵結CD40且刺激受試者以應答疫苗組合物的CD154多肽與其相關的外源抗原性多肽可使用作為免疫刺激性多肽。CD154多肽的長度可為全長CD154或可為少於50個胺基酸，更適當地為少於40、少於30或少於20個胺基酸。多肽的長度可介於10至15個胺基酸之間、介於10至20個胺基酸之間或介於10至25個胺基酸之間。CD154序列與CD40結合區域係在各種物種之間不是高度保留。雞與人類的CD154序列分別地被提供於SEQ ID NO：106與SEQ ID NO：107內。
已經確定了許多物種的CD154的CD40結合區域，包含人類、雞、鴨、小鼠與牛，並分別地參見SEQ ID NO：108、SEQ ID NO：109、SEQ ID NO：110、SEQ ID NO：111與SEQ ID NO：112。也包含與序列SEQ ID NO：106-122所提供的CD154序列相同或至少99%相同、至少98%相同、至少95%相同、至少90%相同、至少85%相同或至少80%相同的多肽。儘管物種之間的CD40結合區域的序列存在變異性，但CD154與CD40的跨物種結合已被報導。舉例而言，人類CD154多肽可增強雞的免疫反應。因此，本發明可使用一種物種特異性CD154多肽或異種CD154多肽實施。
在另一個替代方案中，CD40配位體可為CD40激動性抗體或其部分。此種CD40激動性抗體已至少被揭露於國際申請號WO2015/187969中。數個物種的CD40抗體與激動性CD40抗體也可商業性獲得，特別是小鼠與人類。若抗體可在表達CD40的標靶細胞內誘導信號，則抗體對CD40具有致效性。透過CD40的信號傳導造成抗原表現細胞的表面上的CD40與TNF受體的表現增加並誘導活性含氧物與一氧化氮的產生，且B細胞活化導致同型轉換(isotype switching)。
合適的雞CD40激動性抗體包含本文提供的抗體，如SEQ ID NO：113(重鏈)與稱為2C5的(SEQ IN NO：114(輕鏈)或SEQ ID NO：115(稱為DAG-1的單鍵可變片段(scFv))。此些抗體可以「雞化(chickenized)」形成製造，使得Fc部分與非-CDR區域可被同源宿主相容抗體骨架序列取代，以最小化對於抗體骨架本身的免疫反應。此外，抗體可以重組或是經由酵素消化(即：木瓜酵素或胃蛋白酶)製成抗體的較小部分，且僅包含像是F(ab) 2片段的抗體的F(ab)部分。已識別雞CD40抗體兩者的CDR區域。對於指定為2C5且提供於SEQ ID NO：113與SEQ ID NO：114的抗體，重鏈可變區域包含含有示於SEQ ID NO：116的胺基酸序列的CDR1、含有示於SEQ ID NO：117的胺基酸序列的CDR2與含有示於SEQ ID NO：118的胺基酸序列的CDR3，且輕鏈可變區域包含含有示於SEQ ID NO：119的胺基酸序列的CDR1、含有示於SEQ ID NO：120的胺基酸序列的CDR2與含有示於SEQ ID NO：121的胺基酸序列的CDR3。對於指定為DAG-1且提供於SEQ ID NO：115的抗體，重鏈可變區域包含含有示於SEQ ID NO：122的胺基酸序列的CDR1、含有示於SEQ ID NO：123的胺基酸序列的CDR2與含有示於SEQ ID NO：124胺基酸序列的CDR3，且其中輕鏈可變區域包含含有示於SEQ ID NO：125的胺基酸序列的CDR1、含有示於SEQ ID NO：126的胺基酸序列的CDR2與含有示於SEQ ID NO：127的胺基酸序列的CDR3。也包含與SEQ ID NO：113-127的至少其一相同或至少99%相同、至少98%相同、至少95%相同、至少90%相同、至少85%相同或至少80%相同的多肽。
本文提供的疫苗組合物包含酵母菌。酵母菌可選自任何下述的酵母菌屬：酵母菌屬(Saccharomyces)、念珠菌屬(Candida)、隱球菌屬(Cryptococcus)、漢遜氏菌屬(Hansenula)、克魯維菌屬(Kluyveromyces)、畢赤酵母菌屬(Pichia)、紅酵母菌屬(Rhodotorula)、裂殖酵母菌屬(Schizosaccharomyces)與耶氏酵母菌屬(Yarrowia)。酵母菌可為選自由啤酒酵母菌、白色念珠菌( Candida albicans)、多形漢遜酵母菌( Hansenula polymorpha)、巴斯德畢赤酵母菌與粟酒裂殖酵母菌( Schizosaccharomyces pombe)所組成的群組的物種。使用巴斯德畢赤酵母菌於例子中。酵母菌包含編碼免疫刺激性多肽的免疫刺激性多核苷酸且可進一步包含編碼抗原性多肽的抗原性多核苷酸。合適的免疫刺激性多肽與抗原性多肽本質不被酵母菌天然表達。酵母菌為工程化以表達免疫刺激性多肽與抗原性多肽，且這些多肽顯示或表達於酵母菌的表面上。
抗原性多肽的至少一部份與免疫刺激性多肽的至少一部份呈現於巴斯德畢赤酵母菌或其他酵母菌基底的免疫組合物的表面上。包含於跨膜蛋白且與跨膜蛋白、膜脂或細胞膜GPI-錨定碳水化合物或蛋白質交互作用、共價或化學交聯的多肽呈現於疫苗組合物的表面上。多肽可藉由具有包含透過肽鍵鍵結跨膜蛋白內的N端、C端或任何位置(即：插入跨膜蛋白的兩個胺基酸之間或取代跨膜蛋白的一或多個胺基酸(即，缺失-插入))連結的多肽的胺基酸而被包含於跨膜蛋白中。所屬技術領域中具有通常知識者將理解的是，非天然的免疫刺激性多核苷酸或者抗原性多核苷酸可被插入在跨膜或細胞壁蛋白的細胞外環(extracellular loop)中的框架，以得到免疫刺激性或抗原性多肽的表面表達。在本例中，使用以酵母菌的共價連結GPI錨定系統的α-凝集素C端錨定方法，但對所屬技術領域中具有通常知識者，可利用其他相似之錨定方法。
另外，多肽可以通過對所屬技術領域中具有通常知識者所可利用的方法共價地或化學鍵地與細胞膜內的蛋白、脂質或碳水化合物結合。舉例而言，雙硫鍵或生物素-卵白素交聯能用於呈現在疫苗組合物中的酵母菌的表面上的抗原性或免疫刺激性多肽。適當地，抗原性多肽與免疫刺激性多肽係為融合蛋白的一部分。此兩種多肽可透過肽鍵直接地連結或可藉由插入其中的由多核苷酸編碼的連結子肽(linker peptide)或第三蛋白的部分來分離。在某些實施例中，包含多於一個複製體(copy)的免疫刺激性多肽及/或抗原性多肽的每一個之融合蛋白包含於酵母菌。在某些實施例中，免疫刺激性多肽的多個複製體包含相同的免疫刺激性多肽或不同的多肽的多於一個的複製體。對於抗原性多肽亦是相同，亦即，於酵母菌可包含相同或相似抗原性多肽的多個複製體，例如：可具有單一或僅少數胺基酸序列差異性的多個複製體的禽流感(avian influenza)M2e抗原。或者，酵母菌可工程化以表達多個不同且相異的抗原性多肽，以允許疫苗組合物的單次施予，以誘發或增強對於從不同物種來的不同抗原的免疫反應。舉例而言，疫苗組合物可藉由含有可被包含於相同疫苗組合物的SEQ ID NO：55 與SED ID NO：61的抗原性多肽而製備成增強對於彎曲桿菌屬( Campylobacter)與艾美球蟲屬(Eimeria)的後續感染的免疫反應。
編碼抗原性多肽或免疫刺激性多肽的多核苷酸可被插入至疫苗組合物的酵母菌中，且表達以產生抗原性多肽與免疫刺激性多肽。多核苷酸可被插入至疫苗組合物的染色體中，或編碼於質體或像是於YAC(酵母菌人工染色體)上的其他染色體外DNA。合適地，編碼抗原性多肽及/或免疫刺激性多肽的多核苷酸可獨立地表達或被插入至被表達的酵母菌疫苗多核苷酸中。酵母菌疫苗多核苷酸可編碼表達於像是跨膜蛋白的酵母菌疫苗的表面上的多肽。編碼抗原性多肽及/或免疫刺激性多肽的多核苷酸可被插入至酵母菌疫苗多核苷酸序列，以允許於酵母菌的表面上的抗原性多肽及/或免疫刺激性多肽的表達。
或著，編碼抗原性多肽及/或免疫刺激性多肽的多核苷酸可被插入至透過與酵母菌疫苗表面上的蛋白質、脂質或碳水化合物相關而以顯示或呈現在酵母菌疫苗的表面上的分泌多肽中。所屬技術領域中具有通常知識者將理解的是，編碼抗原性多肽及/或免疫刺激性多肽的多核苷酸可被插入至多種酵母菌多核苷酸，以將抗原性多肽及/或免疫刺激性多肽的表達與呈現提供至以酵母菌治療的受試者的免疫細胞。
如上所述，描述於本文中的疫苗也可包含編碼抗原性多肽的抗原性多核苷酸。抗原性多肽係為可藉由適應性免疫系統特異性地辨認的多肽。抗原性多肽可藉由選擇作為載體的酵母菌天然地表達，以接種針對作為疫苗載體的酵母菌。或者，酵母菌疫苗載體可攜帶作為抗原性多肽而編碼異種多肽且與疫苗載體非天然地結合的異種多核苷酸。抗原性多肽包含任何免疫性多肽。抗原性多肽包含病原體相關的、過敏原相關的、腫瘤相關的或疾病相關的抗原，但不限制於此。病原體包含病毒的、寄生蟲的、真菌的與細菌的病原體以及像是病原性蛋白顆粒(prions)的蛋白質病原體。抗原性多肽可為全長蛋白或其部分。
眾所周知的，許多蛋白質的免疫系統辨認是基於相對低的胺基酸數目，通常被稱為抗原決定位。抗原決定位可為僅8-10個胺基酸。抗原性多肽的用語可包含在受試者中產生的抗體或T細胞免疫反應的抗原決定位。抗原決定位與抗原或抗原性多肽的用語可被互換地使用。因此，描述於本文中的抗原性多肽可為全長蛋白、8個胺基酸長度的抗原決定位或是任何介於此些極值的部分。事實上，抗原性多肽可包含從單一病原體或蛋白質的多於一個抗原決定位。抗原性多肽可包含像是與乳腺炎感染(Mastitis infection)、沙門氏菌屬( Salmonella)、梭菌屬( Clostridium)、彎曲桿菌屬、大腸桿菌屬( Escherichia)、志賀桿菌屬( Shigella)、螺旋桿菌屬( Helicobacter)、弧菌屬( Vibrio)、鄰單胞菌屬( Plesiomonas)、愛德華菌屬( Edwardia)、克雷白氏菌屬( Klebsiella)、葡萄球菌屬( Staphylococcus)、鏈球菌屬( Streptococcus)與產氣單孢菌屬( Aeromonas)相關結的細菌的大片段或小的細菌多肽，但不限制於此；病毒性蛋白質包含流行性感冒(Influenza)、口蹄疫病毒(Foot and Mouth virus)、豬流行性腹瀉病毒(porcine epidemic diarrhea virus，PEDv)以及豬生殖與呼吸綜合症病毒(Porcine reproductive and respiratory syndrome virus，PRRSV)，但不限制於此；寄生蟲感染包含艾美球蟲屬( Eimeriaspp)、弓蟲(Toxoplasma)、瘧疾或其他寄生蟲，但不限制於此；以及腫瘤抗原。舉例而言，可使用於美國專利號8,604,198、國際公開號WO2009/059018、WO2009/059298、WO2011/091255、WO2011/156619、WO2014070709、WO2014/127185或WO2014/152508所識別的抗原或抗原決定位。抗原性多肽可包含提供於SEQ ID NO：39-93中的任一或多個，且可包含與提供於SEQ ID NO：39-93的至少一種相同或至少99%相同、至少98%相同、至少95%相同、至少90%相同、至少85%相同或至少80%相同的多肽。所屬領域中具有通常知識者認知到，包含於SEQ ID NO：39-93的部分多肽比可能需要作為抗原決定位的多肽更長，因此此些抗原性多肽的片段也包含於本文中，所屬領域中具有通常知識者也認知到，抗原性多肽也可包含額外的胺基酸，或可彼此連接或藉由連結子胺基酸(linker amino acids)連接免疫刺激性多肽，以形成一種融合蛋白。連結子胺基酸可為任何胺基酸，但是最常使用絲胺酸與甘胺酸。連結子可以短至一個或兩個胺基酸，但長度可以為4、5、6、8、10、12、14、15或更多個胺基酸。
相同抗原決定位或抗原性多肽的多個複製或從不同蛋白質來的多個抗原決定位可被包含於疫苗載體中。可以設想的是，來自相同或不同病原體或疾病的多個抗原決定位或抗原可被施用於在酵母菌疫苗載體的組合物中，以產生對抗多個抗原的增強的免疫反應。酵母菌疫苗載體可編碼從多個致病微生物、病毒或與腫瘤相關抗原的抗原。可表達多個抗原的疫苗載體的施予具有同時誘導對於兩個或多個疾病的免疫的優點。
編碼可增強對於抗原性多肽的免疫反應的免疫刺激性多肽的多核苷酸也可編碼抗原性多肽。編碼免疫刺激性多肽的多核苷酸可被連接至編碼抗原性多肽的多核苷酸，以使在疫苗載體內的免疫刺激性多肽與抗原性多肽藉由相同的多核苷酸編碼。至少一部份的抗原性多肽與免疫刺激性多肽呈現在酵母菌疫苗載體的表面上。疫苗組合物可包含編碼抗原性多肽的抗原性多核苷酸及編碼免疫刺激性多肽的免疫刺激性多核苷酸。例如在融合蛋白中，免疫刺激性多肽與抗原性多肽可被連接。免疫刺激性多肽與抗原性多肽可皆被插入至跨膜蛋白的外環中，或可透過GPI-錨定機制被接附至表面。
異種多核苷酸包含編碼選自酵母菌疫苗載體以外的致病微生物或病毒的抗原的多核苷酸，但不限於此。此異種或抗原性多核苷酸可衍生自像是流感(例如：M2e、血球凝集素(hemagglutinin)或神經胺糖酸苷酶(neuraminidase))、皰疹病毒(herpesviruses)(例如：編碼皰疹病毒結構蛋白的基因)、反轉錄病毒(retroviruses)(例如：gp260包膜蛋白)、腺病毒(adenoviruses)、副黏病毒(paramyxoviruses)、冠狀病毒(coronaviruses)等的致病性病毒。異種多核苷酸也可從例如：編碼像是毒素的細菌蛋白及外膜蛋白的基因的致病性細菌獲得。再者，來自像是艾美球蟲的寄生蟲的異種多核苷酸係用於酵母菌載體的疫苗組合物的有利候選物。
本文所述的疫苗組合物也可包含涉及觸發免疫系統的其他免疫刺激性多肽。多核苷酸可編碼針對其刺激作用而已知的免疫系統分子，像是介白素(interleukin)、腫瘤壞死因子(Tumor Necrosis Factor)或干擾素(interferon,)或像是CD40配位體或CD40致效劑的關於免疫調節的其他多肽。因此，酵母菌疫苗載體可包含多於一種免疫刺激性多肽或多於一種抗原性多肽。其包含多於一種複製體的相同多肽，以增加多肽表達水平。或者，多個不同的免疫刺激性多肽或編碼相同或多個抗原性多肽的核苷酸或編碼其的核苷酸可包含於單一個重組酵母菌中。多個抗原性多肽可係像是M2e抗原的兩個不同的抗原決定位(SEQ ID NO：41與42)的相似抗原的多個複製體。抗原性多肽可為針對完全不同的抗原但與相同致病原相關的相關，例如M2e與HA5。參見SEQ ID NO：41-44。抗原性多肽也可為針對不同物種的抗原，以便用單一單體疫苗(single unitary vaccine)接種對抗多於一種病原體。例如將針對流感M2e的SEQ ID NO：41與針對來自 E. coli的PAL的SEQ ID NO：54或針對來自艾美球蟲的MPP的SEQ ID NO：61組合。在範例中，產生包含表達MPP-TRAP-HMGB-1 (SEQ ID NO: 61連接至SEQ ID NO: 65連接至SEQ ID NO: 2)的酵母菌的疫苗組合物，並顯示減少與因巨型艾美球蟲的造成相關的發病率與死亡率。
也提供包含疫苗組合物與藥學上可接受的載體的組合物。藥學上可接受的載體係適用於體內( in vivo)施用的任何載體。適當地，藥學上可接受的載體可用於口服、鼻用或黏膜遞輸。藥學上可接受的載體可包含水、緩衝溶液、葡萄糖溶液或細菌培養液。組合物的額外成分可適當地包含像是穩定劑、防腐劑、稀釋劑、乳化劑與潤滑劑的賦形劑。藥學上可接受的載體或稀釋劑的實例包含像是碳水化合物(例如：山梨糖醇、甘露糖醇、澱粉、蔗糖、葡萄糖、葡聚醣)的穩定劑、像是白蛋白或酪蛋白的蛋白質、像是牛血清或脫脂牛乳以及緩衝液(例如：磷酸鹽緩衝液)的含蛋白試劑。特別是當將這些穩定劑加入至組合物中時，組合物適用於冷凍乾燥或噴霧乾燥。
疫苗組合物可不在受試者內複製。酵母菌可不能在實驗室外的環境成長，像是酵母菌的減毒形式。適當地，酵母菌在加入疫苗組合物之前是失活的或死亡的。疫苗組合物也可包含佐劑。佐劑為所屬技術領域中已知，且在實施例中使用甘露糖化的幾丁聚醣佐劑。參見WO 2014/070709。
本文所述的組合物可用於增強免疫反應，像是對於抗原性多肽或對於疫苗載體本身的抗體反應。本文所述的組合物與疫苗載體可藉由降低疾病的持續時間、降低與疾病相關的發病率或死亡率或是降低感染疾病的可能性，以減少後續疾病的嚴重性。與未提供疫苗載體的相似受試者相較，在施用本文所述的疫苗載體後，與疾病相關的發病率或死亡率可降低25%、30%、40%、50%、60%、 70%、80%、90% 或甚至100%。
也提供藉由施用疫苗組合物而增強受試者的免疫反應的方法。疫苗組合物可包含可刺激對疫苗組合物以及其相關的抗原性多肽的免疫反應的全長免疫刺激性多肽或其部分。包含免疫刺激性多肽的疫苗組合物以有效增強受試者對疫苗，特別是抗原性多肽的免疫反應的量施用於受試者。增強的免疫反應包含誘導藉由受試者的免疫系統介導的治療或預防作用，但不限於於此。該作用可藉由測試對於抗原性多肽或表達抗原性多肽的傳染性或致癌試劑的應答來測量。具體而言，增強免疫反應可包含增強抗體的製造、增強抗體重鏈的類型轉換(class switching)、抗原呈現細胞的成熟、輔助T細胞的刺激、溶細胞性T細胞的刺激或T及/或B細胞記憶的誘導，但不限於此。
組合物可藉由各種方式施用，包含皮下、口服、鼻內與黏膜，但不限於此。舉例而言，疫苗組合物或疫苗載體可藉由氣溶膠、噴霧劑、於食物或水中添加、口服胃管灌食或經由點眼劑遞輸。在一些實施例中，組合物藉由像是皮內、腸胃外、皮下、腹膜內、靜脈內、顱內或肌肉注射以施用。對於雞或是其他家禽，組合物可以卵內( in ovo)施用。也可使用組合施用方式。在實例中，在皮下疫苗接種之後，以口服疫苗組合物加強。也可使用其他組合，例如，經由氣溶膠傳輸或噴霧經鼻或遞輸之後，口服胃管灌食或包涵在飼料或飲用水中。
受試者包含脊椎動物，合適地為哺乳動物，合適地為人、牛、貓、狗、豬；水產，合適地為鯰魚、鯛魚、金魚；或鳥類，合適地為像是雞或火雞的家禽，但不限於此。也可使用其動物感染模型。增強免疫反應包含誘導藉由受試者的免疫系統介導的治療或預防作用，但不限於此。具體地，增強免疫反應可包含增強抗體的產生，如第4圖與第5圖所示。在一些實施例中，產生IgA應答。
所施用的有效劑量根據受試者的年紀、體重與物種、施用的方式與途徑以及針對尋求免疫反應的病原體或疾病的類型而改變。組合物可以足以引起免疫反應的酵母菌疫苗載體的任何劑量施用。可以預見的是，10 5至10 10個酵母菌載體複製體的劑量範圍係為足夠。具體地，藉由在400X放大倍率下使用血球計計算酵母菌於立方mm下的數量所定義的10 8劑量的巴斯德畢赤酵母菌-HMGB1疫苗載體的複製體為最適化，以用於誘導疫苗載體特異性免疫反應，其最終表示對於酵母菌細胞表面上與HMGB1相鄰的抗原性物質(antigenic cargo)的免疫反應的刺激。
組合物可僅施用一次，或可施用兩次或更多次以增加免疫反應。如果組合物施用多於一次，則如上所述每次施用疫苗時，可以通過不同的施用途徑施用組合物。舉例而言，組合物可間隔一星期、兩星期或三星期、一個月、兩個月、三個月、六個月或更長時間而施用兩次或兩次以上。酵母菌在施用之前可為活菌，但在大部分實施例中，酵母菌在施用前將被殺滅或失活。在一些實施例中，酵母菌可能夠在受試者內複製，而在其他實施例中，酵母菌可不能在受試者內複製。如實例所示，酵母菌疫苗載體可於施用前，使用福馬林(formalin)、戊二醛(glutaraldehyde)、乙醇、酸化、加熱或抗生素而失活。所屬領域中具有通常知識者將理解的是，也可使用其他用以失活酵母菌疫苗載體的方法。
本揭露不限於本文所述的組件的構造、設置或方法步驟的具體細節。根據下述揭露，對於所屬領域中具有通常知識者而言顯而易見的是本文所揭露的組合物與方法可以各種形式製造、實踐、使用、實施及/或形成。本文使用的用語與術語僅用於描述之目的，不應被認為對於申請專利範圍的範疇的限制。在描述和申請專利範圍內中用於代表各種結構或方法步驟的序數指示詞，像是第一、第二與第三，不代表著被解釋為表示任何特定的結構或步驟，或任何特定順序或像是結構或步驟的配置。除非本文另有說明或著與上下文明顯矛盾，本文所述的所有方法可以任何適合的順序執行。除非另有說明，本文提供的任何與所有實例或例示性語言(例如：「例如 (such as )」的使用僅旨在促進揭露，並且不表示對本揭露的範疇的任何限制。說明書內的任何語言以及附圖所示的任何結構不應被解釋為表示對於實施揭露的標的為必要的任何未請求的元件。本文所使用的術語「包含 (including)」、「包含(comprising)」或「具有(having)」與其變形意在包含其後列出的元件及其等效物，以及附加元件。描述為「包含(including)」、「包括(comprising)」或「具有(having)」特定元件的實施例也被認為是此些特定元件「實質上由…組成(consisting essentially of)」或「由…組成(consisting of )」。
除非本文另有說明，本文中數值的範圍的描述僅旨在用作落在範圍內的每個單獨數值的各自提及的簡寫方法，並將每個單獨的數值併入本說明書，如同在本文中的單獨列舉一樣。舉例而言，若濃度範圍表示為1%至50%，其意為像是2%至40%、10%至30%或1%至3%等的數值明確列舉於本說明書內。這些僅為具體意圖的實例，且包含且在考慮列舉的最低值與最高值之間的數值的所有可能的組合在本揭露中被明確地陳述。用語「約(about)」的使用以描述特定列舉的數量或數量的範圍且表示數值非常接近包含在該數量中的所列數量，像是可由於或本質上由於製造公差、形成測量中的儀器與人為錯誤等而考慮的值。除非另有說明，所有參照數量的百分比係重量百分比。
不承認任何參考文獻，包含於說明書內引用的任何非專利或專利文件構成先前技術。特別地，將理解的是，除非另有說明，否則本文提及的任何文件不構成承認任何此些文件形成美國或任何其他國家中的所屬技術領域中的通常知識的不部分。參考文獻的任何討論都說明其作者的主張，且申請人保留質疑本文引用的任何文件的準確性和相關性的權利。除非另有明確的說明，本文引用的所有參考文獻皆併入本文作為參考。本揭露將控制在引用的參考文獻中找到的任何定義及/或描述之間存在任何差異。
下述實例僅表示說明性，並不表示著對本發明或所附申請專利範圍的範疇的限制。
實例
我們開發了一種表達全長高遷移率族蛋白1(HMGB1)的巴斯德畢赤酵母菌疫苗載體，以顯著增加對於抗原性物質的免疫反應。先前，我們將截短的CD154或CD40配位體、多肽及/或全長HMGB1插入制雙重減毒的腸炎沙門氏菌(SE)，並藉由Raw264鼠類巨噬細胞比較SE的吞噬細胞的攝取(第1圖)。使用螢光激發細胞分選儀(FACS)分析測量在Raw264內的相對螢光強度。螢光強度是因為在較酸pH值下的金黃色葡萄球菌( S. aureus)的pHrodo指示劑粒子上的螢光信號增強來測量。一旦細菌因吞噬作用而被巨噬細胞攝入，在吞噬細胞內產生吞噬溶酶體(phagolysosome)。巨噬細胞藉由酸化吞噬溶酶體內的pH值以分解細菌。因此，積極分解細菌的巨噬細胞會具有更大的螢光強度。第1圖內的數據表示，與減毒的SE疫苗載體單獨比較，鼠類巨噬細胞優先地吞噬含有HMGB1的SE疫苗載體(P=0.011)，且CD154不顯著改變鼠類巨噬細胞的吞噬攝入(P=0.057)。
我們已經使用質體整合系統，將巴斯德畢赤酵母菌工程化以用於細胞表面表達HMGB1，以將HMGB1蛋白染色體插入於巴斯德畢赤酵母菌中，增強對於疫苗物質的免疫反應。巴斯德畢赤酵母菌相較於啤酒酵母菌產生10至100倍大的蛋白質表達。HMGB1發送危險訊號至觸發RAGE應答的免疫系統。上述吞噬作用測定顯示，HMGB1係為可增加載體系統的攝入，舉例而言，將腸炎沙門氏菌攝入至鼠類巨噬細胞內的有效的免疫刺激性分子。酵母菌細胞表面上的HMGB1表達應藉由如在腸炎沙門氏菌建構體中所觀察到的吞噬作用來增強酵母菌載體疫苗被攝入至巨噬細胞。我們從Invitrogen®獲得的EasySelect畢赤酵母菌表達套組( PichiaExpression Kit)，其包含用於在巴斯德畢赤酵母菌內表達的pPICZ 表達載體。目前尚不存在巴斯德畢赤酵母菌的細胞表面表達套組，但是幾個研究者已使用GPI錨定蛋白質來啟動在酵母菌系統內的細胞表面表達(Wasilenko et al., 2009)。所使用的GPI錨定蛋白質係來自啤酒酵母菌的α凝集素的C端部分。藉由絲胺酸間隔物區接合至pPICZ細胞內表達質體而將HMGB1連接至酵母菌α凝集素的C端部分(第2圖與SEQ ID NO：1)。pPICZ係一種用於快速高效的蛋白質表達的甲醇誘導型質體。第3圖證實HMGB1的細胞表面表達，其顯示僅於轉化酵母菌細胞上呈現HMGB1的免疫螢光(第3E圖與第3F圖)。
在確認HMGB1蛋白表達於巴斯德畢赤酵母菌的細胞表面上後，我們選擇三個HMGB1陽性巴斯德畢赤酵母菌株以在肉雞(n=15隻雛雞/組)中測試。在無菌水中使用0.3% 戊二醛以使巴斯德畢赤酵母菌-HMGB1陽性株#3、4與6失活，並在甘露糖化幾丁聚醣佐劑中以1：2混合。參見WO 2014/070709，其全部內容於此併入本文作為參考。我們藉由皮下注射0.25mL疫苗/雛雞施予每個巴斯德畢赤酵母菌-HMGB1陽性建構體的10 7至10 9的三種劑量(表1)。在孵化日與第14天接種肉雞。在第21天收集用於測量IgG抗體效價的血清。在我們實驗室中最佳化測量對巴斯德畢赤酵母菌的IgG特異性的直接ELISA。所報告的樣品/陰性控制組血清比用以測定ELISA鑑定中盤對盤的變異性。從每隻肉雞定義對於巴斯德畢赤酵母菌特異性的抗體效價。接種巴斯德畢赤酵母菌-HMGB1的雛雞的IgG與接種未修飾的巴斯德畢赤酵母菌(X33)的雛雞的IgG進行比較。比較結果如第4圖所示。
表1：於肉雞雛雞中的巴斯德畢赤酵母菌接種劑量策略
  組別 劑量
1 控制組-無巴斯德畢赤酵母菌 (Control-No Pichia pastoris) -
2 巴斯德畢赤酵母菌w/o HMGB1 (X33) 10 7
3 巴斯德畢赤酵母菌 -HMGB1 3 10 7
4 巴斯德畢赤酵母菌-HMGB1 4 10 7
5 巴斯德畢赤酵母菌-HMGB1 6 10 7
6 巴斯德畢赤酵母菌-HMGB1 (X33) 10 8
7 巴斯德畢赤酵母菌-HMGB1 3 10 8
8 巴斯德畢赤酵母菌-HMGB1 4 10 8
9 巴斯德畢赤酵母菌-HMGB1 6 10 8
10 巴斯德畢赤酵母菌-HMGB1 (X33) 10 9
11 巴斯德畢赤酵母菌-HMGB1 3 10 9
12 巴斯德畢赤酵母菌 -HMGB1 4 10 9
13 巴斯德畢赤酵母菌 -HMGB1 6 10 9
然後，我們用巴斯德畢赤酵母菌-HMGB1建構體#3、4與6接種三週大的肉雞，以確定是否觀察到類似的IgG抗體反應。我們用0.25mL的每個巴斯德畢赤酵母菌疫苗接種三週大的肉雞(表1：n=10隻肉雞/組)。在無菌水中使用0.3%戊二醛使巴斯德畢赤酵母-HMGB1陽性建構體#3、4與6失活，並在甘露糖化幾丁聚醣佐劑中以1：2混合。肉雞在第21天與第35天接種疫苗。第21天收集用於IgG抗體效價測量的血清。在我們實驗室中最佳化測量對巴斯德畢赤酵母菌的IgG特異性的直接ELISA。所報告的在450 nm的吸光度以未接種的肉雞(群組1)進行標準化，用以測定ELISA鑑定中盤對盤的變異性。從每隻肉雞定義對於巴斯德畢赤酵母菌特異性的抗體效價。接種巴斯德畢赤酵母菌-HMGB1的雛雞的IgG與接種修飾的巴斯德畢赤酵母菌(X33)的雛雞的IgG進行比較。比較結果如第5圖所示。
與注射未修飾的巴斯德畢赤酵母菌相較，在以SQ注射失活的HMGB1+巴斯德畢赤酵母菌的肉雞內，HMGB1顯著地提升對於巴斯德畢赤酵母菌特異性的IgG抗體效價(第4圖與第5圖)。HMGB1增加對於巴斯德畢赤酵母菌疫苗載體的免疫反應，其表示藉由相同巴斯德畢赤酵母菌表達的任何抗原性物質將引起比沒有HMGB1的巴斯斯德畢赤酵母菌內表達的抗原性物質更高的免疫反應。
材料與方法
作為Easy Select TM畢赤酵母菌表達套組的一部分，從Invitrogen(Carlsbad, CA, USA)獲得巴斯德畢赤酵母菌X33(野生型)。藉由Genscript(Piscataway, NJ, USA)合成在巴斯德畢赤酵母菌內表達最佳化的HMGB1編碼序列，並應用至本實驗室的pUC57選殖載體。在疫苗建構期間，TOP10電穿孔的大腸桿菌(Invitrogen)用於所有需要的質體增殖。使用質體DNA轉化後，使用含有100 µg/mL的盤尼西林(Ampicillin)的LB培養基或含有50µg/mL吉歐黴素(Zeocin)的低鹽LB培養基，使大腸桿菌在37 oC下增殖。當合適時，在30 oC下使用含有50µg 吉歐黴素YPD培養基進行巴斯德畢赤酵母菌的常規增殖。含有組胺酸(MMH)的酵母菌基本培養基(minimal medium)與含有葡萄糖(MDH)的酵母菌基本培養基被用於重組疫苗株的後續篩選。含有甘油(GSY)的基本培養基與含有甲醇(MM)的基本培養基被用於誘導培養中的巴斯德畢赤酵母菌的HMGB1表達。
疫苗載體的建構
為了製備巴斯德畢赤酵母菌-HMGB1表達載體，使用 KpnI與 PmeI消化pPICZ以製備用於轉殖的載體骨架。將pUC57/HMGB1-α凝集素以 KpnI與 EcoRV消化，且隨後將1.6kb HMGB1-α凝集素插入物用膠體純化。在進行連接並轉化至TOP10大腸桿菌後，進行菌落PCR以識別攜帶適當連接pPICZ/HMGB1-α凝集素的質體的菌落。於Easy Select TM套組內提供PCR的引子，AOXSeqF(5’ GACTGGTTCCAATTGACAAGC 3’；SEQ ID NO: 128)；AOXSeqR(5’ GCAAATGGCATTCTGACATCC 3’；SEQ ID NO: 129)。使用KOD DNA聚合酶(Millipore；Darmstadt， Germany)產生擴增子。該反應的循環參數如下述：98 oC，10分鐘，隨後為98 oC，15秒；55 oC，55秒循環25次。在阿肯色大學DNA核心實驗室(Fayetteville，AR)進行定序，以進一步驗證連接質體pPICZ/HMGB1-α凝集素。隨後，pPICZ/HMGB1-α凝集素藉由 PmeI消化作用而線性化，並純化以製備用於巴斯德畢赤酵母菌X-33的電穿孔。
對於電穿孔，將5 mL 的巴斯德畢赤酵菌X33置於YPD培養液(broth)中，在30 oC生長過夜。第二天，用500毫升的新鮮YPD培養液接菌5mL的培養物，並生長至OD為1.5。接著，用冰冷的無菌水洗滌細胞兩次，且用冰冷的無菌山梨糖醇(1M)洗滌一次。細胞最終再懸浮於1mL的冰冷的山梨糖醇中。80微升的勝任細胞巴斯德畢赤酵母菌與10µg的線性化pPICZ/HMGB1-α凝集素混合，並在2.0KV下脈衝一次以電穿孔酵母菌細胞。在含有100µg/mL 吉歐黴素的YPD盤上，選擇含有吉歐黴素抗性基因的線性疫苗建構體的經歷成功的染色體整合的轉化體。再次使用菌落PCR以分析轉化體。使用前述的引子與循環參數。
巴斯德畢赤酵母菌pPICZ/HMGB1 AOX1基因的篩選
測試所得的疫苗株以驗證驅動HMGB1-α凝集素的表達所需的AOX1基因的存在與穩定性。藉由塗盤在MDH與MMH洋菜膠上來測試除了GS115 Mut(在Easy Select TM畢赤酵母菌表達套組中提供具有非功能性 AOX1基因的陰性控制株)以外的9種吉歐黴素抗性菌株。AOX1缺陷株顯示在MMH培養基的生長相較在MDH上慢很多。在此兩種培養基上的生長時間被用於識別 AOX1缺陷株。9種菌株中的每一種外加陰性控制組GS115 Mut被重複地塗盤在MMH與MDH培養基上，並培養3天。每24小時確認一次培養物，並記錄生長程度。
HMGB1-α凝集素蛋白質誘導
為了在培養物中誘導HMGB1的表達，將從單一菌落的50mL的巴斯德畢赤酵母菌pPICZ/HMGB1-α凝集素培養物於MGY培養液中，在30 oC生長過夜。25毫升的此過夜培養物被轉置於250mL或預熱過的MM培養液中，並以滅菌的紗布覆蓋以適當通氣。接著，此培養物以劇烈搖動(250rpm)中生長96小時，每24小時加入100%甲醇至最終濃度為0.5%，以維持誘導。在96小時後，HMGB1-α凝集素基因產物的誘導最大化。
誘導後，9種巴斯德畢赤酵母菌-HMGB1陽性建構體的每一個使用免疫螢光測試測試於巴斯德畢赤酵母菌細胞表面上的HMGB1蛋白表達。使用於磷酸鹽緩衝溶液(PBS)中以1：5比例稀釋的兔多株HMGB1 156-177以及與1%山羊血清PBS中以1：1000比例的與Alexa 488共軛的山羊抗兔IgG的F(ab) 2部分染色巴斯德畢赤酵母菌-HMGB1建構體#1、3、4、5、6、7、8、9及10與X33骨架。在被轉化的9個巴斯德畢赤酵母菌-HMGB1建構體中的3個(#3、4與6)上，最佳地表達HMGB1蛋白表達。
接種酵母菌載體疫苗候選物後的腸炎沙門氏菌恢復的評估
在刺激(challenge)後，我們接下來測試酵母菌載體PAL-HMGB1(SEQ ID ：54連接至SEQ ID NO：2)與抗體引導PAL疫苗候選物對於減少腸炎沙門氏菌(SE)，亦即血清群D沙門氏菌(serogroup D Salmonella)的恢復的功效。在家禽場孵化60隻SPF來亨雞。在孵化日，雛雞被分為兩組，控制組或接種組。接種組的雛雞用4.25 x 10 9cfu/鳥酵母菌-PAL-HMGB1皮下接種疫苗與經口灌食，接著將兩組放置於有網面地板的層架式雞籠中，並提供任食的飼料與水。在接種疫苗前，將用於取樣的十隻1天大的雛雞藉由CO 2吸入安樂死，以確認雛雞係沙門氏菌陰性反應。在第7天，接種疫苗的雞用5 x 10 9cfu/鳥以皮下接種疫苗與經口灌食加強。在第14天，所有的雞藉由經口灌食1.2 x 10 8cfu/鳥的SE進行刺激。在第21天與第28天，獲得每組的10個泄殖腔檢體(cloacal swabs)以評估功毒菌株的脫落。在第32天，從20隻雞(控制組)或10隻雞(接種組)收集肝臟、脾臟(LS)與盲腸(CT)，並藉由直接塗盤(CFU/g)培樣與富集SE發生率的程度。
實驗流程的結論
群組編號 (n=30) 群組 接種劑量 DOH 加強劑量 D7 刺激劑量 D14 泄殖腔檢體
1 控制組 NA NA SE@10 8/bird D21, 28
2 酵母菌-PAL-HMGB1-SC/經口 10 9/ml 10 9/ml SE@10 8/bird D21, 28
結果：
如表2所示，刺激後18天，從接種酵母菌-PAL-HMGB-1疫苗的雞中明顯回復較少的沙門氏菌。如表3所示，從泄殖腔檢體也明顯回復較少的沙門氏菌，且於刺激後2週內完全消除。
表2、刺激後18天的SE回復
  LS (%+) CT (% + (# +))
控制組 0 65 (13/20)
酵母菌-PAL-HMGB1 0 30 (3/10)*
*與控制組的差異 p＜0.1
表3、刺激後1週與2週從泄殖腔檢體的SE回復
  1 wk (% + (# +)) 2 wk (% + (# +))
控制組 70 (14/20) 25 (5/20)
酵母菌-PAL-HMGB1 40 (4/10) 0 (0/10)*
*與控制組的差異p＜0.1
接種酵母菌載體的疫苗候選物後的球蟲感染評估
在刺激後，我們接下來測試酵母菌(巴斯德畢赤酵母菌)載體MPP-TRAP-HMGB1(SEQ ID NO：61連接至SEQ ID NO：65連接至SEQ ID NO：2)對於降低艾美球蟲M6品系的感染後的發病率與死亡率的功效。從商業孵化場獲得孵化當天的80隻雛雞。孵化當天，雛雞被隨機分成四組，陰性控制組、陽性控制組、在孵化日與第14天以經口灌食接種在MCA疫苗中的畢赤酵母菌-MPP-TRAP-HMGB1或在第4天與第14天置入飲用水中以接種在MCA疫苗中的畢赤酵母菌-MPP-TRAP-HMGB1。接種疫苗的雛雞藉由經口灌食或置於飲用水中，以5 x 10 7cfu/鳥的酵母菌-MPP-TRAP-HMGB1接種。甘露糖化的幾丁聚醣佐劑(MCA)儲存溶液(1.5%幾丁聚醣 w：v)與畢赤酵母菌的分散液(0.5%最終濃度)以1：2稀釋。對於經口灌食，以0.25mL遞輸MCA(0.5%)加上畢赤酵母菌建構體(1x10 7細胞)以用於初次(prime)及加強兩者的經口灌食。對於飲用水的施用，MCA在飲用水內的最終濃度為0.004%，且畢赤酵母菌的最終濃度為2.3 x 10 6細胞/mL飲用水，且此用於初次與加強施用兩者。所有的雛雞被單獨地標記，且除了飲用水接種的期間外，混合所有的雛雞(N=20 每組)，且提供任食的飼料與水。
所有組別在第20天被刺激，且在接種後第6天測定病變評分。一些卵囊從初始刺激中逃脫(他們維持不變)，所以在這些混合的雛雞中在未刺激控制組中預計會有很小的刺激。在第20天，用100,000巨型艾美球蟲(品系M6)卵囊刺激陽性控制鳥類與兩組接種疫苗的鳥類。在第26天，每隻鳥用Johnson及Reid病變評分(Johnson and Reid Lesion score)指標評分病變。Johnson, J. and W. M. Reid 1970. Experimental Parasitology 28: 30-36。在此病變評分方法中，鑑定數值分數如下述：0：整體無病變；1：小的紅色皮下血斑可出現在中腸漿膜側，儘管可出現少量的橘色黏液，此處沒有腸道腫脹或增厚；2：漿膜表面可出現許多紅色皮下血斑，腸道充滿橘色黏液，少量或沒有腸道腫脹，腸壁變厚；3：腸壁腫脹且增厚，黏膜表面粗糙，腸道內容物充滿微小的血塊與黏液；4：腸壁的大部分長度可腫脹，含有許多血塊與產生特徵顏色與腐敗的氣味的消化紅血球；腸壁大幅增厚，死掉的鳥類以此分數紀錄。
第6圖顯示刺激後第6天具有病變評分為4的動物的百分比率，且每條柱狀中指示的百分比率顯示刺激後第6天的死亡率百分比。值得注意的是，相較於15%的陽性控制組動物，接種疫苗的鳥類沒有一隻在第6天死亡。如第6圖所示，由計算的p值顯示病變評分也被降低(飲用水接種的p= 0.037，經口灌食的p= 0.067)。當隨著作為免疫刺激性多肽的HMGB1與表達MPP及TRAP抗原兩者的畢赤酵母菌包含於飲用水中時，病變評分顯著降低。統計分析如下進行。使用在SAS中的PROC MIXED ANOVA模式分析病變數據，假設介於分數0與1之間的嚴重程度差異與介於分數1與2之間的嚴重程度的差異相似，以此類推。在此假設下，可分析PROC MIXED ANOVA分析的評分方法。如Johnson及Reid (1970)所述，病變評分的範圍從0到4。執行隨機與固定效應的測試。計算不同方法以定義介於治療組內病變評分之間的任何顯著差異。數據定義成具有帕松分布(Poisson distribution)，且利用Tukey Kramer 測試用於定義介於治療組之間是否存在任何統計上顯著差異。
如第7圖所示，在接種疫苗的動物中，所有病變評分的分布也減少。接種疫苗的動物證實較低的病變評分。因此，在飲用水中或經由口服灌食接種疫苗，使得在艾美球蟲刺激後的死亡率較低且發病率較低。
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第1圖係為比較與具螢光標記的腸炎沙門氏菌( SalmonellaEnteriditis) aroA/ htrA、腸炎沙門氏菌 aroA/ htrA-AgA-CD154與腸炎沙門氏菌 aroA/ htrA-AgA-AgB-HMGB1共培養後的RAW264巨噬細胞的螢光強度圖。
第2圖係為設計成包含於巴斯德畢赤酵母菌( Pichia pastoris)上使用多醣磷脂肌醇 (glycosylphosphatidylinositol) 錨定啤酒酵母菌α凝集素 (Saccharomyces cerevisiae alpha agglutinin) 細胞表面表達方法的雞( Gallus gallus)特異性的高遷移率族蛋白1(high mobility group box 1，HMGB1)表達的pPICZ質體圖譜的示意圖。pPICZ係使用甲醇可誘導的AOX1啟動子。
第3圖係為顯示於巴斯德畢赤酵母菌(X33)上的HMGB1細胞表面表達的一組照片。巴斯德畢赤酵母菌-HMGB1建構體#4(第3D圖：僅DIC；第3E圖：僅螢光；第3F圖：DIC/螢光疊圖)與巴斯德畢赤酵母菌(X33；第3A圖：僅DIC；第3B圖：僅螢光；第3C圖：DIC/螢光疊圖)骨架使用於磷酸鹽緩衝溶液(PBS)中以1：5稀釋的兔多株HMGB1 156-177(rabbit polyclonal HMGB1 156-177)以及與1：1000比例於1%山羊血清PBS中的Alexa 488共軛的山羊抗兔(goat anti-rabbit)IgG的F(ab) 2部分染色。HMGB1蛋白質表達係最佳化地表達於轉化的九個巴斯德畢赤酵母菌-HMGB1建構體中的三個。
第4圖係為顯示巴斯德畢赤酵母菌特異性血清抗體樣品/陰性控制組血清比率的圖式。我們觀察到使用ELISA鑑定的巴斯德畢赤酵母菌特異性抗體的典型劑量反應曲線。以10 7/肉雞(broiler) SQ施予的巴斯德畢赤酵母菌對於免疫反應量太少，且施用10 9/肉雞係為太多而甚至導致X33建構體骨架的血清轉化。以10 8/肉雞 SQ施予的巴斯德畢赤酵母菌係為最佳劑量，其可使所有HMGB1+巴斯德畢赤酵母菌建構體顯著地提升巴斯德畢赤酵母菌特異性血清抗體(P＜0.001)。
第5圖係顯示對於未接種的控制組肉雞(組1)之血清比率標準化之巴斯德畢赤酵母菌特異性血清抗體的圖式。我們預期的劑量反應為可再現的。我們觀察到典型劑量反應曲線。以10 7/肉雞SQ施予的巴斯德畢赤酵母菌對於免疫反應量太少，且施用10 9/肉雞係為太多而甚至導致連X33建構體骨架的血清轉化。以10 8/肉雞 SQ施予的巴斯德畢赤酵母菌係為最佳劑量，其使所有HMGB1+巴斯德畢赤酵母菌建構體顯著地提升巴斯德畢赤酵母菌特異性血清抗體(P=0.049)。
第6圖係為顯示施打後第6天具有病變評分為4的動物的百分比率，且在每條柱狀中指示的百分比率顯示施打後第6天的死亡率百分比的圖式。
第7圖係為顯示在接種疫苗的動物中所有病變評分的分布也減少的圖式。接種疫苗的動物表現出較低的病變評分。
 
<![CDATA[<110>  阿肯色州大學董事會 The Board Of Trustees Of The University Of Arkansas]]>
                 美國德州Ａ＆Ｍ大學系統中心 The Texas A&amp;&lt; University System]]&gt;
          <br/><![CDATA[       
          <![CDATA[<120>  包含免疫刺激性及抗原性多肽的酵母菌疫苗載體以及其使用方法]]>
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              130                 135                 140                 
          Lys Ser Lys Lys Lys Lys Glu Glu Glu Asp Asp Glu Glu Asp Glu Glu 
          145                 150                 155                 160 
          Asp Glu Glu Glu Glu Glu Glu Glu Glu Asp Glu Asp Glu Glu Glu Asp 
                          165                 170                 175     
          Asp Asp Asp Glu 
                      180 
          <![CDATA[<210>  8]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  恆河獼猴 (Macaca mulatta)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  8]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  9]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  食蟹獼猴 (Macaca fascicularis)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  9]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  10]]>
          <![CDATA[<211>  227]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  小耳大嬰猴 (Otolemur garnettii)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(227)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  10]]>
          Met Asp Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Cys 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Gly Glu Glu Arg Glu Lys Lys His 
                      20                  25                  30          
          Pro Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu 
                  35                  40                  45              
          Arg Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met 
              50                  55                  60                  
          Ala Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile 
          65                  70                  75                  80  
          Pro Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro 
                          85                  90                  95      
          Lys Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro 
                      100                 105                 110         
          Lys Ile Lys Gly Glu His His Leu Ser Thr Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Ser Asn Pro Ala Ala Gly Asp Lys Gln Pro Glu 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Glu Glu Lys Asp Lys Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Val Gly Ser Ser Arg Leu Lys Lys 
                          165                 170                 175     
          Ala Arg Lys Arg Arg Lys Arg Arg Lys Met Arg Lys Met Lys Arg Lys 
                      180                 185                 190         
          Lys Met Met Asn Lys Leu Val Leu Ala Gln Phe Leu Phe Leu Val Tyr 
                  195                 200                 205             
          Lys Ala Phe Asn Pro Leu Val Tyr Asn Ser Leu Leu Leu Lys Lys Lys 
              210                 215                 220                 
          Ile Glu Met 
          225         
          <![CDATA[<210>  11]]>
          <![CDATA[<211>  211]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  非洲爪蟾 (Xenopus laevis)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(211)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  11]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ala Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Ser Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Val Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Ser Thr Ile Gly Asp Ile Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Thr Asp Asp Lys Leu Pro Phe 
              130                 135                 140                 
          Glu Arg Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Val Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Glu Pro Ala Lys Lys Ala Pro Ala 
                          165                 170                 175     
          Lys Pro Glu Lys Ala Lys Lys Lys Glu Glu Asp Asp Glu Asp Asp Asp 
                      180                 185                 190         
          Glu Glu Asp Glu Asp Glu Glu Asp Glu Glu Glu Glu Glu Glu Glu Asp 
                  195                 200                 205             
          Asp Asp Glu 
              210     
          <![CDATA[<210>  12]]>
          <![CDATA[<211>  211]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  熱帶爪蟾 (Xenopus (Silurana) tropicalis)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(211)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  12]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ala Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Ser Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Val Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Ser Thr Ile Gly Asp Ile Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Thr Asp Asp Lys Leu Pro Tyr 
              130                 135                 140                 
          Glu Arg Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Val Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Glu Pro Ala Lys Lys Ala Pro Ala 
                          165                 170                 175     
          Lys Phe Glu Lys Ala Lys Lys Lys Glu Asp Asp Asp Asp Asp Glu Asp 
                      180                 185                 190         
          Asp Asp Asp Glu Glu Glu Glu Asp Glu Glu Glu Glu Asp Glu Glu Asp 
                  195                 200                 205             
          Asp Asp Glu 
              210     
          <![CDATA[<210>  13]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  東非狒狒 (Papio Anubis)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  13]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  14]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  毛腮伶猴 (Callicebus moloch)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  14]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  15]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  狨 (Callithrix jacchus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  15]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  16]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  家牛 (Bos Taurus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  16]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Glu Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  17]]>
          <![CDATA[<211>  214]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  印度牛 (Bos indicus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(214)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  17]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Lys 
                          165                 170                 175     
          Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu Asp 
                      180                 185                 190         
          Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Glu Glu Glu 
                  195                 200                 205             
          Glu Asp Asp Asp Asp Glu 
              210                 
          <![CDATA[<210>  18]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  家馬 (Equus caballus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  18]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  19]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  家犬 (Canis lupus familiaris)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  19]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  20]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  野豬 (Sus scrofa)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  20]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys His Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Glu Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  21]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  穴兔 (Oryctolagus cuniculus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  21]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu 
                      180                 185                 190         
          Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200                 205             
          Glu Glu Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  22]]>
          <![CDATA[<211>  206]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  紅擬石首魚 (Sciaenops ocellatus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(206)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  22]]>
          Met Val Lys Glu Gln Gly Lys Pro Arg Gly Lys Met Ser Ser Tyr Ala 
          1               5                   10                  15      
          Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Asp 
                      20                  25                  30          
          Ala Ser Val Asn Phe Ala Glu Phe Ser Lys Lys Cys Ser Gly Arg Trp 
                  35                  40                  45              
          Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Leu Ala Arg 
              50                  55                  60                  
          Gln Asp Lys Ala Arg Tyr Glu Arg Glu Met Met Ser Tyr Val Pro Ala 
          65                  70                  75                  80  
          Arg Gly Gly Lys Lys Lys Lys Tyr Lys Asp Pro Asn Ala Pro Lys Arg 
                          85                  90                  95      
          Pro Pro Ser Ala Phe Phe Ile Phe Cys Ser Glu Phe Arg Pro Lys Val 
                      100                 105                 110         
          Lys Gly Glu Ala Pro Gly Leu Thr Ile Gly Glu Val Ala Lys Arg Leu 
                  115                 120                 125             
          Gly Glu Met Trp Asn Gly Thr Ala Ser Glu Asp Lys Gln Pro Phe Glu 
              130                 135                 140                 
          Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Glu Val Ala Ala 
          145                 150                 155                 160 
          Tyr Arg Gln Lys Thr Lys Ala Gly Ala Gly Pro Ala Ala Lys Ala Pro 
                          165                 170                 175     
          Ala Lys Val Glu Lys Lys Val Glu Asp Asp Asp Asp Asp Asp Asp Asp 
                      180                 185                 190         
          Asp Glu Glu Glu Glu Glu Asp Asp Tyr Asp Asp Asp Asp Glu 
                  195                 200                 205     
          <![CDATA[<210>  23]]>
          <![CDATA[<211>  182]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  斑點叉尾鮰(Ictalurus punctatus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(182)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  23]]>
          Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Asp Thr Ser Val 
          1               5                   10                  15      
          Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg Trp Lys Thr Met 
                      20                  25                  30          
          Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala Arg Leu Asp Lys 
                  35                  40                  45              
          Ala Arg Tyr Glu Arg Glu Met Lys Asn Tyr Val Pro Pro Arg Gly Glu 
              50                  55                  60                  
          Lys Lys Lys Arg Phe Lys Asp Pro Asn Ala Pro Lys Arg Pro Pro Ser 
          65                  70                  75                  80  
          Ala Phe Phe Ile Phe Cys Ala Glu Tyr Arg Pro Lys Val Lys Glu Glu 
                          85                  90                  95      
          Thr Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys Leu Gly Glu Met 
                      100                 105                 110         
          Trp Asn Lys Thr Ser Ala Glu Glu Lys Gln Pro Tyr Glu Lys Lys Ala 
                  115                 120                 125             
          Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala Ala Tyr Arg Lys 
              130                 135                 140                 
          Gly Lys Val Val Gly Gly Ala Ala Lys Ala Pro Thr Lys Pro Asp Lys 
          145                 150                 155                 160 
          Ala Asp Asp Asp Glu Asp Asp Asp Asp Asp Glu Asp Asp Asp Asp Asp 
                          165                 170                 175     
          Asp Asp Glu Asp Asp Glu 
                      180         
          <![CDATA[<210>  24]]>
          <![CDATA[<211>  209]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  紅笛鯛 (Lutjanus sanguineus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(209)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  24]]>
          Met Gly Arg Glu Pro Arg Glu Pro Gly Lys Pro Arg Gly Lys Met Ser 
          1               5                   10                  15      
          Ser Tyr Ala Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys 
                      20                  25                  30          
          His Pro Asp Ala Ser Val Asn Phe Ala Glu Phe Ser Lys Lys Cys Ser 
                  35                  40                  45              
          Glu Arg Trp Lys Thr Met Ser Pro Lys Glu Lys Ser Lys Phe Glu Asp 
              50                  55                  60                  
          Leu Ala Arg Gln Asp Lys Ala Arg Tyr Glu Arg Glu Met Leu Thr Tyr 
          65                  70                  75                  80  
          Val Pro Ala Arg Gly Gly Lys Lys Lys Lys Phe Lys Asp Pro Asn Ala 
                          85                  90                  95      
          Pro Lys Arg Pro Pro Ser Ala Phe Phe Ile Phe Cys Ser Glu Phe Arg 
                      100                 105                 110         
          Pro Lys Val Lys Gly Glu Ser Pro Gly Leu Ser Ile Gly Glu Val Ala 
                  115                 120                 125             
          Lys Arg Leu Gly Glu Met Trp Asn Gly Thr Ser Ser Glu Asp Lys Gln 
              130                 135                 140                 
          Pro Phe Glu Lys Lys Ala Ala Lys Leu Lys Glu Arg Tyr Glu Lys Glu 
          145                 150                 155                 160 
          Val Ala Ala Tyr Arg Gln Lys Thr Lys Gly Gly Ser Ala Pro Ala Gly 
                          165                 170                 175     
          Lys Ala Pro Ala Lys Ala Glu Lys Lys Val Glu Glu Asp Asp Asp Asp 
                      180                 185                 190         
          Glu Glu Asp Asp Asp Asp Glu Glu Glu Glu Asp Tyr Asp Asp Asp Asp 
                  195                 200                 205             
          Glu 
          <![CDATA[<210>  25]]>
          <![CDATA[<211>  204]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  鯽魚 (Carassius auratus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(204)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  25]]>
          Met Gly Lys Asp Pro Thr Lys Pro Arg Gly Lys Met Ser Ser Tyr Ala 
          1               5                   10                  15      
          Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Glu 
                      20                  25                  30          
          Ala Thr Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg Trp 
                  35                  40                  45              
          Lys Thr Met Ser Gly Lys Glu Lys Gly Lys Phe Glu Asp Met Ala Lys 
              50                  55                  60                  
          Gln Asp Lys Val Arg Tyr Glu Arg Glu Met Lys Asn Tyr Ile Pro Pro 
          65                  70                  75                  80  
          Lys Gly Glu Lys Lys Lys Arg Phe Lys Asp Pro Asn Ala Pro Lys Arg 
                          85                  90                  95      
          Pro Pro Ser Ala Phe Phe Ile Phe Cys Ser Glu Phe Arg Ser Lys Val 
                      100                 105                 110         
          Lys Glu Glu Thr Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Arg Leu 
                  115                 120                 125             
          Gly Glu Met Trp Asn Lys Thr Ser Ala Glu Asp Lys Gln Pro Phe Glu 
              130                 135                 140                 
          Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala Ala 
          145                 150                 155                 160 
          Tyr Arg Ser Lys Gly Lys Val Val Gly Gly Ala Ala Lys Ala Pro Ser 
                          165                 170                 175     
          Lys Pro Val Lys Val Asn Asp Asp Asp Asp Asp Asp Asp Glu Asp Glu 
                      180                 185                 190         
          Asp Glu Asp Asp Asp Asp Glu Glu Glu Asp Asp Glu 
                  195                 200                 
          <![CDATA[<210>  26]]>
          <![CDATA[<211>  198]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  大西洋鮭魚 (Salmo salar)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(198)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  26]]>
          Met Gly Lys Asp Pro Arg Lys Pro Arg Gly Lys Met Ser Ser Tyr Ala 
          1               5                   10                  15      
          Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Glu 
                      20                  25                  30          
          Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg Trp 
                  35                  40                  45              
          Arg Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Leu Ala Lys 
              50                  55                  60                  
          Leu Asp Lys Val Arg Tyr Glu Arg Glu Met Arg Ser Tyr Ile Pro Pro 
          65                  70                  75                  80  
          Lys Gly Glu Lys Lys Lys Arg Phe Lys Asp Pro Asn Ala Pro Lys Arg 
                          85                  90                  95      
          Pro Ser Ser Ala Phe Phe Ile Phe Cys Ala Asp Phe Arg Pro Gln Val 
                      100                 105                 110         
          Lys Gly Glu Thr Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys Leu 
                  115                 120                 125             
          Gly Glu Lys Trp Asn Asn Leu Thr Ala Glu Asp Lys Val Pro Tyr Glu 
              130                 135                 140                 
          Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Thr Ala 
          145                 150                 155                 160 
          Tyr Arg Asn Lys Gly Lys Val Pro Val Ser Val Pro Ala Lys Ala Ala 
                          165                 170                 175     
          Ala Pro Thr Lys Asp Asp Asp Asp Asp Asp Asp Asp Asp Asp Asp Asp 
                      180                 185                 190         
          Glu Asp Asp Asp Asp Asp 
                  195             
          <![CDATA[<210>  27]]>
          <![CDATA[<211>  206]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  銀鱈 (Anoplopoma fimbria)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(206)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  27]]>
          Met Val Lys Glu Leu Gly Lys Pro Lys Gly Lys Met Ser Ser Tyr Ala 
          1               5                   10                  15      
          Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Glu 
                      20                  25                  30          
          Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg Trp 
                  35                  40                  45              
          Lys Thr Met Ser Leu Lys Glu Lys Gly Lys Phe Glu Asp Leu Ala Arg 
              50                  55                  60                  
          Gln Asp Lys Ala Arg Tyr Glu Arg Glu Met Met Ser Tyr Ile Pro Pro 
          65                  70                  75                  80  
          Arg Gly Ile Lys Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys Arg 
                          85                  90                  95      
          Pro Pro Ser Ala Phe Phe Ile Phe Cys Ala Glu Tyr Arg Pro Lys Val 
                      100                 105                 110         
          Lys Gly Glu Thr Pro Gly Ala Thr Ile Gly Asp Val Ala Lys Arg Leu 
                  115                 120                 125             
          Gly Glu Met Trp Asn Gly Thr Ala Ser Glu Asp Arg Gln Pro Phe Glu 
              130                 135                 140                 
          Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Glu Val Ala Ala 
          145                 150                 155                 160 
          Tyr Arg Ala Lys Thr Lys Pro Gly Ala Cys Ala Ala Ala Ala Pro Ser 
                          165                 170                 175     
          Lys Ala Pro Ala Lys Val Glu Lys Lys Val Glu Asp Asp Asp Asp Asp 
                      180                 185                 190         
          Asp Asp Asp Glu Glu Glu Asp Asp Phe Asp Asp Asp Asp Asp 
                  195                 200                 205     
          <![CDATA[<210>  28]]>
          <![CDATA[<211>  194]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  虹鱒 (Oncorhynchus mykiss)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(194)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  28]]>
          Met Gly Lys Asp Pro Arg Lys Pro Arg Gly Lys Met Ser Ser Tyr Ala 
          1               5                   10                  15      
          Tyr Phe Val Gln Thr Cys Arg Ala Glu His Lys Lys Lys His Pro Glu 
                      20                  25                  30          
          Ala Ser Val Asn Phe Ala Glu Phe Ser Lys Lys Cys Ser Glu Arg Trp 
                  35                  40                  45              
          Lys Pro Met Ser Pro Lys Glu Lys Gly Lys Phe Glu Asp Met Ala Lys 
              50                  55                  60                  
          Gln Asp Lys Val Arg Tyr Glu Gly Glu Met Lys Asn Tyr Ile Pro Pro 
          65                  70                  75                  80  
          Asn Gly Gln Lys Lys Lys Arg Phe Lys Asp Pro Asn Ala Pro Lys Arg 
                          85                  90                  95      
          Pro Pro Ser Ala Phe Phe Ile Phe Cys Ala Asp Phe Arg Ala Lys Ile 
                      100                 105                 110         
          Lys Ser Glu His Pro Gly Leu Ser Ile Gly Asp Thr Ala Lys Lys Leu 
                  115                 120                 125             
          Gly Val Met Trp Asn Ser Ser Ala Ala Glu Glu Lys Lys Pro Tyr Glu 
              130                 135                 140                 
          Lys Lys Ala Ala Thr Leu Lys Glu Lys Tyr Asp Lys Asp Ile Ala Ser 
          145                 150                 155                 160 
          Tyr Arg Thr Asn Gly Arg Val Asp Thr Ala Ser Ser Ala Ala Ala Asp 
                          165                 170                 175     
          Asp Glu Glu Glu Asp Asp Glu Glu Asp Asp Asp Glu Asp Glu Asp Asp 
                      180                 185                 190         
          Asp Glu 
          <![CDATA[<210>  29]]>
          <![CDATA[<211>  208]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  七鰓鰻 (Lethenteron camtschaticum)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(208)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  29]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Lys Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys Asn Pro 
                      20                  25                  30          
          Glu Ala Ser Val Asn Phe Ala Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Glu Lys Glu Lys Thr Arg Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Val Asp Lys Val Arg Tyr Asp Arg Glu Met Lys Thr Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Arg Gly Ser Arg Lys Lys Lys Asp Pro Asn Ala Pro 
                          85                  90                  95      
          Lys Arg Pro Pro Ser Ala Phe Phe Ile Tyr Cys Ala Glu Tyr Arg Ser 
                      100                 105                 110         
          Lys Val Arg Ala Glu Asn Pro Gly Leu Thr Ile Gly Ser Ile Ala Lys 
                  115                 120                 125             
          Lys Leu Gly Glu Met Trp Asn Asn Ala Pro Ala Asp Glu Lys Ser Ile 
              130                 135                 140                 
          Tyr Glu Arg Lys Thr Ala Lys Leu Lys Glu Lys Tyr Asp Lys Asp Met 
          145                 150                 155                 160 
          Ala Ser Tyr Arg Ser Lys Gly Lys Val Glu Thr Ser Lys Val Ala Ser 
                          165                 170                 175     
          Lys Pro Ala Ser Lys Gln Arg Asp Asp Asp Asp Asp Glu Asp Asp Asp 
                      180                 185                 190         
          Glu Asp Glu Asp Glu Asp Glu Asp Glu Asp Asp Asp Asp Asp Asp Glu 
                  195                 200                 205             
          <![CDATA[<210>  30]]>
          <![CDATA[<211>  172]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  草魚(Ctenopharyngodon idella)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(172)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  30]]>
          Met Gly Lys Asp Pro Arg Lys Pro Lys Gly Lys Met Ser Ser Tyr Ala 
          1               5                   10                  15      
          Tyr Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Glu 
                      20                  25                  30          
          Ala Thr Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg Trp 
                  35                  40                  45              
          Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala Lys 
              50                  55                  60                  
          Gln Asp Lys Val Arg Phe Glu Arg Glu Met Lys Asn Tyr Ile Pro Pro 
          65                  70                  75                  80  
          Lys Gly Glu Lys Lys Arg Arg Phe Lys Asp Pro Asn Ala Pro Lys Arg 
                          85                  90                  95      
          Pro Pro Ser Ala Phe Phe Ile Phe Cys Gly Asp Tyr Arg Pro Lys Ile 
                      100                 105                 110         
          Arg Gly Glu Asn Pro Gly Leu Ser Ile Gly Asp Ile Ala Lys Lys Leu 
                  115                 120                 125             
          Gly Glu Met Trp Asn Ser Ser Ser Ala Glu Val Lys Gln Pro Tyr Glu 
              130                 135                 140                 
          Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Asp Lys Asp Ile Ala Leu 
          145                 150                 155                 160 
          Tyr Arg Thr Lys Gly Ile Ala Gly Leu Ser Lys Lys 
                          165                 170         
          <![CDATA[<210>  31]]>
          <![CDATA[<211>  106]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  眼鏡王蛇 (Ophiophagus Hannah)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(106)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  31]]>
          Met Ala Lys Ala Asp Lys Val Arg Tyr Asp Arg Glu Met Lys Asp Tyr 
          1               5                   10                  15      
          Gly Pro Ala Lys Gly Gly Lys Lys Lys Lys Asp Pro Asn Ala Pro Lys 
                      20                  25                  30          
          Arg Pro Pro Ser Gly Phe Phe Leu Phe Cys Ser Glu Phe Cys Ser Glu 
                  35                  40                  45              
          Phe Arg Pro Lys Ile Lys Ser Thr Asn Pro Gly Ile Ser Ile Gly Asp 
              50                  55                  60                  
          Val Ala Lys Lys Leu Gly Glu Met Trp Asn Asn Leu Ser Asp Ser Glu 
          65                  70                  75                  80  
          Lys Gly Pro Tyr Asn Asn Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu 
                          85                  90                  95      
          Lys Val Arg Leu Gly Cys Trp Cys Trp Cys 
                      100                 105     
          <![CDATA[<210>  32]]>
          <![CDATA[<211>  51]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  豐年蝦 (Artemia franciscana)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(51)]]>
          <![CDATA[<223>  HMGB1]]>
          <![CDATA[<400>  32]]>
          Met Pro Arg Ser Lys Asp Glu Ser Lys Pro Arg Gly Lys Leu Thr Ala 
          1               5                   10                  15      
          Tyr Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Arg Lys His 
                      20                  25                  30          
          Pro Asp Glu Asn Val Val Phe Ala Glu Phe Ser Lys Lys Cys Ala Glu 
                  35                  40                  45              
          Arg Trp Lys 
              50      
          <![CDATA[<210>  33]]>
          <![CDATA[<211>  85]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(85)]]>
          <![CDATA[<223>  HMGB1盒a1]]>
          <![CDATA[<400>  33]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr 
                          85  
          <![CDATA[<210>  34]]>
          <![CDATA[<211>  54]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(54)]]>
          <![CDATA[<223>  HMGB1盒a2]]>
          <![CDATA[<400>  34]]>
          Pro Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu 
          1               5                   10                  15      
          Arg Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met 
                      20                  25                  30          
          Ala Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val 
                  35                  40                  45              
          Pro Pro Lys Gly Glu Thr 
              50                  
          <![CDATA[<210>  35]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(73)]]>
          <![CDATA[<223>  HMGB1盒b1]]>
          <![CDATA[<400>  35]]>
          Lys Asp Pro Asn Ala Pro Lys Arg Pro Pro Ser Ala Phe Phe Leu Phe 
          1               5                   10                  15      
          Cys Ser Glu Phe Arg Pro Lys Ile Lys Gly Glu His Pro Gly Leu Ser 
                      20                  25                  30          
          Ile Gly Asp Val Ala Lys Lys Leu Gly Glu Met Trp Asn Asn Thr Ala 
                  35                  40                  45              
          Ala Asp Asp Lys Gln Pro Tyr Glu Lys Lys Ala Ala Lys Leu Lys Glu 
              50                  55                  60                  
          Lys Tyr Glu Lys Asp Ile Ala Ala Tyr 
          65                  70              
          <![CDATA[<210>  36]]>
          <![CDATA[<211>  69]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(69)]]>
          <![CDATA[<223>  HMGB1盒b2]]>
          <![CDATA[<400>  36]]>
          Asn Ala Pro Lys Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu 
          1               5                   10                  15      
          Phe Arg Pro Lys Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp 
                      20                  25                  30          
          Val Ala Lys Lys Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp 
                  35                  40                  45              
          Lys Gln Pro Tyr Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu 
              50                  55                  60                  
          Lys Asp Ile Ala Ala 
          65                  
          <![CDATA[<210>  37]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(21)]]>
          <![CDATA[<223>  HMGB1 RAGE 結合位(binding domain)]]>
          <![CDATA[<400>  37]]>
          Lys Asp Pro Asn Ala Pro Lys Arg Pro Pro Ser Ala Phe Phe Leu Phe 
          1               5                   10                  15      
          Cys Ser Glu Phe Arg 
                      20      
          <![CDATA[<210>  38]]>
          <![CDATA[<211>  33]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(33)]]>
          <![CDATA[<223>  HMGB1促發炎細胞介素活性]]>
          <![CDATA[<400>  38]]>
          Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala Ala Tyr Arg Ala Lys Gly 
          1               5                   10                  15      
          Lys Val Asp Ala Gly Lys Lys Val Val Ala Lys Ala Glu Lys Ser Lys 
                      20                  25                  30          
          Lys 
          <![CDATA[<210>  39]]>
          <![CDATA[<211>  182]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(182)]]>
          <![CDATA[<223>  產氣莢膜梭菌 (Clostridium perfringens)抗原]]>
          <![CDATA[<400>  39]]>
          Ser Lys Glu Tyr Ala Arg Gly Phe Ala Lys Thr Gly Lys Ser Ile Tyr 
          1               5                   10                  15      
          Tyr Ser His Ala Ser Met Ser His Ser Trp Asp Asp Trp Asp Tyr Ala 
                      20                  25                  30          
          Ala Lys Val Thr Leu Ala Asn Ser Gln Lys Gly Thr Ala Gly Tyr Ile 
                  35                  40                  45              
          Tyr Arg Phe Leu His Asp Val Ser Glu Gly Asn Asp Pro Ser Val Gly 
              50                  55                  60                  
          Lys Asn Val Lys Glu Leu Val Ala Tyr Ile Ser Thr Ser Gly Glu Lys 
          65                  70                  75                  80  
          Asp Ala Gly Thr Asp Asp Tyr Met Tyr Phe Gly Ile Lys Thr Lys Asp 
                          85                  90                  95      
          Gly Lys Thr Gln Glu Trp Glu Met Asp Asn Pro Gly Asn Asp Phe Met 
                      100                 105                 110         
          Thr Gly Ser Lys Asp Thr Tyr Thr Phe Lys Leu Lys Asp Glu Asn Leu 
                  115                 120                 125             
          Lys Ile Asp Asp Ile Gln Asn Met Trp Ile Arg Lys Arg Lys Tyr Thr 
              130                 135                 140                 
          Ala Phe Pro Asp Ala Tyr Lys Pro Glu Asn Ile Lys Val Ile Ala Asn 
          145                 150                 155                 160 
          Gly Lys Val Val Val Asp Lys Asp Ile Asn Glu Trp Ile Ser Gly Asn 
                          165                 170                 175     
          Ser Thr Tyr Asn Ile Lys 
                      180         
          <![CDATA[<210>  40]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(6)]]>
          <![CDATA[<223>  CPa的保護性抗原決定位 (protective epitope)]]>
          <![CDATA[<400>  40]]>
          Ala Arg Gly Phe Ala Lys 
          1               5       
          <![CDATA[<210>  41]]>
          <![CDATA[<211>  8]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  禽流感 (Avian Influenza)病毒]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(8)]]>
          <![CDATA[<223>  禽流感病毒m2e]]>
          <![CDATA[<400>  41]]>
          Glu Val Glu Thr Pro Ile Arg Asn 
          1               5               
          <![CDATA[<210>  42]]>
          <![CDATA[<211>  8]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  禽流感病毒]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(8)]]>
          <![CDATA[<223>  禽流感病毒m2e]]>
          <![CDATA[<400>  42]]>
          Glu Val Glu Thr Pro Thr Arg Asn 
          1               5               
          <![CDATA[<210>  43]]>
          <![CDATA[<211>  12]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  禽流感病毒]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(12)]]>
          <![CDATA[<223>  禽流感病毒(HA5 UA)]]>
          <![CDATA[<400>  43]]>
          Leu Leu Ser Arg Ile Asn His Phe Glu Lys Ile Gln 
          1               5                   10          
          <![CDATA[<210>  44]]>
          <![CDATA[<211>  19]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  禽流感病毒]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(19)]]>
          <![CDATA[<223>  禽流感病毒(HA5 LB)]]>
          <![CDATA[<400>  44]]>
          Ala Asn Pro Ala Asn Asp Leu Cys Tyr Pro Gly Asp Phe Asn Asp Tyr 
          1               5                   10                  15      
          Glu Glu Leu 
          <![CDATA[<210>  45]]>
          <![CDATA[<211>  16]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  禽流感病毒]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(16)]]>
          <![CDATA[<223>  禽流感病毒(NP 54-69)]]>
          <![CDATA[<400>  45]]>
          Gly Arg Leu Ile Gln Asn Ser Ile Thr Ile Glu Arg Met Val Leu Ser 
          1               5                   10                  15      
          <![CDATA[<210>  46]]>
          <![CDATA[<211>  14]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  禽流感病毒]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(14)]]>
          <![CDATA[<223>  禽流感病毒(NP 147-160)]]>
          <![CDATA[<400>  46]]>
          Thr Tyr Gln Arg Thr Arg Ala Leu Val Arg Thr Gly Met Asp 
          1               5                   10                  
          <![CDATA[<210>  47]]>
          <![CDATA[<211>  19]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  大腸桿菌 (E. coli)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(19)]]>
          <![CDATA[<223>  從大腸桿菌獲得的PAL bis]]>
          <![CDATA[<400>  47]]>
          Glu Gly His Ala Asp Glu Arg Gly Thr Pro Glu Tyr Asn Ile Ser Leu 
          1               5                   10                  15      
          Gly Glu Arg 
          <![CDATA[<210>  48]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的胜肽]]>
          <![CDATA[<400>  48]]>
          Gly His Ala Asp Glu Arg 
          1               5       
          <![CDATA[<210>  49]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的胜肽]]>
          <![CDATA[<400>  49]]>
          Asp Glu Arg Gly Thr Pro 
          1               5       
          <![CDATA[<210>  50]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的胜肽]]>
          <![CDATA[<400>  50]]>
          Glu Tyr Asn Ile Ser Leu 
          1               5       
          <![CDATA[<210>  51]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的胜肽]]>
          <![CDATA[<400>  51]]>
          Ile Ser Leu Gly Glu Arg 
          1               5       
          <![CDATA[<210>  52]]>
          <![CDATA[<211>  19]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  弧菌 (Vibrio spp.)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(19)]]>
          <![CDATA[<223>  從弧菌 (Vibrio spp.)獲得的PALbis ]]>
          <![CDATA[<400>  52]]>
          Glu Gly His Ala Asp Glu Arg Gly Thr Pro Glu Tyr Asn Ile Ala Leu 
          1               5                   10                  15      
          Gly Glu Arg 
          <![CDATA[<210>  53]]>
          <![CDATA[<211>  17]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  曲狀桿菌 (Campylobacter spp.)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(17)]]>
          <![CDATA[<223>  從曲狀桿菌 (Campylobacter spp.)獲得的對應胜肽]]>
          <![CDATA[<400>  53]]>
          Glu Gly Asn Cys Asp Glu Trp Gly Thr Asp Glu Tyr Asn Gln Ala Leu 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210>  54]]>
          <![CDATA[<211>  19]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  大腸桿菌 (E. coli)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(19)]]>
          <![CDATA[<223>  從大腸桿菌 (E. coli)獲得的PAL]]>
          <![CDATA[<400>  54]]>
          Thr Val Glu Gly His Ala Asp Glu Arg Gly Thr Pro Glu Tyr Asn Ile 
          1               5                   10                  15      
          Ser Leu Gly 
          <![CDATA[<210>  55]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  空腸曲桿菌 (Campylobacter jejuni)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(21)]]>
          <![CDATA[<223>  空腸彎曲桿菌 (Campylobacter jejuni) Cj0113]]>
          <![CDATA[<400>  55]]>
          Gly Val Ser Ile Thr Val Glu Gly Asn Cys Asp Glu Trp Gly Thr Asp 
          1               5                   10                  15      
          Glu Tyr Asn Gln Ala 
                      20      
          <![CDATA[<210>  56]]>
          <![CDATA[<211>  19]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  弧菌 (Vibrio spp.)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(19)]]>
          <![CDATA[<223>  弧菌 (Vibrio spp.) 替代性 PAL 抗原決定位]]>
          <![CDATA[<400>  56]]>
          Thr Val Glu Gly His Ala Asp Glu Arg Gly Thr Pro Glu Tyr Asn Ile 
          1               5                   10                  15      
          Ala Leu Gly 
          <![CDATA[<210>  57]]>
          <![CDATA[<211>  57]]>
          <![CDATA[<212>  DNA]]>
          <![CDATA[<213>  大腸桿菌 (E. coli)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(57)]]>
          <![CDATA[<223>  用為PAL抗原決定位的大腸桿菌 (E. coli)核苷酸序列]]>
          <![CDATA[<400>  57]]>
          gaaggtcacg cggacgaacg tggtaccccg gaatacaaca tctctctggg tgaacgt          57
          <![CDATA[<210>  58]]>
          <![CDATA[<211>  9]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  大腸桿菌 (E. coli)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(9)]]>
          <![CDATA[<223>  從大腸桿菌 (E. coli)獲得的PAL的抗原決定位]]>
          <![CDATA[<400>  58]]>
          Glu Tyr Asn Ile Ser Leu Gly Glu Arg 
          1               5                   
          <![CDATA[<210>  59]]>
          <![CDATA[<211>  9]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  弧菌 (Vibrio spp.)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(9)]]>
          <![CDATA[<223>  從弧菌 (Vibrio spp.)獲得的PAL抗原決定位]]>
          <![CDATA[<400>  59]]>
          Glu Tyr Asn Ile Ala Leu Gly Glu Arg 
          1               5                   
          <![CDATA[<210>  60]]>
          <![CDATA[<211>  16]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：複合最小化抗原決定位]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (2)..(6)]]>
          <![CDATA[<223>  Xaa 可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (13)..(13)]]>
          <![CDATA[<223>  Xaa 可為任何天然存在的胺基酸]]>
          <![CDATA[<400>  60]]>
          Pro Xaa Xaa Xaa Xaa Xaa Gly Tyr Gly Ala Cys Glu Xaa Asn Leu Gly 
          1               5                   10                  15      
          <![CDATA[<210>  61]]>
          <![CDATA[<211>  43]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  巨型艾美球蟲 (Eimeria maxima)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(43)]]>
          <![CDATA[<223>  MPP; 巨型艾美球蟲 (Eimeria maxima)]]>
          <![CDATA[<400>  61]]>
          Pro Ser His Asp Ala Pro Glu Ser Glu Arg Thr Pro Arg Val Ile Ser 
          1               5                   10                  15      
          Phe Gly Tyr Gly Ala Cys Glu His Asn Leu Gly Val Ser Leu Phe Arg 
                      20                  25                  30          
          Arg Glu Glu Thr Lys Lys Asp Pro Arg Gly Arg 
                  35                  40              
          <![CDATA[<210>  62]]>
          <![CDATA[<211>  28]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  犬新包蟲 (Neospora canium)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(28)]]>
          <![CDATA[<223>  犬新包蟲 (Neospora canium)]]>
          <![CDATA[<400>  62]]>
          Pro Arg Ile Val Ser Phe Gly Tyr Gly Ala Cys Glu His Asn Leu Gly 
          1               5                   10                  15      
          Met Ser Leu Tyr Asp Arg Gln Gly Leu Gln Arg Gln 
                      20                  25              
          <![CDATA[<210>  63]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  盲腸型球蟲 (Eimeria tenella)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(21)]]>
          <![CDATA[<223>  盲腸型球蟲 (Eimeria tenella)]]>
          <![CDATA[<400>  63]]>
          Glu Ser Gln Arg Ala Pro Met Val Ile Arg Tyr Gly Tyr Gly Ala Cys 
          1               5                   10                  15      
          Glu Tyr Asn Leu Gly 
                      20      
          <![CDATA[<210>  64]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  巨型艾美球蟲 (Eimeria maxima)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(10)]]>
          <![CDATA[<223>  巨型艾美球蟲 (Eimeria maxima) TRAP-1]]>
          <![CDATA[<400>  64]]>
          Gly Gly Gly Phe Pro Thr Ala Ala Val Ala 
          1               5                   10  
          <![CDATA[<210>  65]]>
          <![CDATA[<211>  40]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  巨型艾美球蟲 (Eimeria maxima)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(40)]]>
          <![CDATA[<223>  巨型艾美球蟲 (Eimeria maxima) TRAP-02]]>
          <![CDATA[<400>  65]]>
          Ala Ala Pro Glu Thr Pro Ala Val Gln Pro Lys Pro Glu Glu Gly His 
          1               5                   10                  15      
          Glu Arg Pro Glu Pro Glu Glu Glu Glu Glu Lys Lys Glu Glu Gly Gly 
                      20                  25                  30          
          Gly Phe Pro Thr Ala Ala Val Ala 
                  35                  40  
          <![CDATA[<210>  66]]>
          <![CDATA[<211>  40]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  巨型艾美球蟲 (Eimeria maxima)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(40)]]>
          <![CDATA[<223>  巨型艾美球蟲 (Eimeria maxima) TRAP-03]]>
          <![CDATA[<400>  66]]>
          Gly Gly Gly Phe Pro Thr Ala Ala Val Ala Gly Gly Val Gly Gly Val 
          1               5                   10                  15      
          Leu Leu Ile Ala Ala Val Gly Gly Gly Val Ala Ala Phe Thr Ser Gly 
                      20                  25                  30          
          Gly Gly Gly Ala Gly Ala Gln Glu 
                  35                  40  
          <![CDATA[<210>  67]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  空腸曲桿菌 (Campylobacter jejuni)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(21)]]>
          <![CDATA[<223>  空腸曲桿菌 (Campylobacter jejuni) Cj0982]]>
          <![CDATA[<400>  67]]>
          Lys Asp Ile Val Leu Asp Ala Glu Ile Gly Gly Val Ala Lys Gly Lys 
          1               5                   10                  15      
          Asp Gly Lys Glu Lys 
                      20      
          <![CDATA[<210>  68]]>
          <![CDATA[<211>  35]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  空腸曲桿菌 (Campylobacter jejuni)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(35)]]>
          <![CDATA[<223>  空腸曲桿菌 (Campylobacter jejuni) Cj0420]]>
          <![CDATA[<400>  68]]>
          Lys Val Ala Leu Gly Val Ala Val Pro Lys Asp Ser Asn Ile Thr Ser 
          1               5                   10                  15      
          Val Glu Asp Leu Lys Asp Lys Thr Leu Leu Leu Asn Lys Gly Thr Thr 
                      20                  25                  30          
          Ala Asp Ala 
                  35  
          <![CDATA[<210>  69]]>
          <![CDATA[<211>  16]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(16)]]>
          <![CDATA[<223>  產氣莢膜梭菌 (Clostridium perfringens) α毒素]]>
          <![CDATA[<400>  69]]>
          Asn Ala Trp Ser Lys Glu Tyr Ala Arg Gly Phe Ala Lys Thr Gly Lys 
          1               5                   10                  15      
          <![CDATA[<210>  70]]>
          <![CDATA[<211>  9]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  禽流感 (Avian influenza)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(9)]]>
          <![CDATA[<223>  禽流感 (Avian influenza) M2e 胜肽]]>
          <![CDATA[<400>  70]]>
          Cys Glu Val Glu Thr Pro Thr Arg Asn 
          1               5                   
          <![CDATA[<210>  71]]>
          <![CDATA[<211>  9]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(9)]]>
          <![CDATA[<223>  1-Alpha-31]]>
          <![CDATA[<400>  71]]>
          Gly Lys Ile Asp Gly Thr Gly Thr His 
          1               5                   
          <![CDATA[<210>  72]]>
          <![CDATA[<211>  15]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(15)]]>
          <![CDATA[<223>  2-Alpha-51]]>
          <![CDATA[<400>  72]]>
          Glu Asn Asp Met Ser Lys Asn Glu Pro Glu Ser Val Arg Lys Asn 
          1               5                   10                  15  
          <![CDATA[<210>  73]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  3-Alpha-71]]>
          <![CDATA[<400>  73]]>
          Glu Asn Met His Glu Leu Gln Leu Gly Ser Thr Tyr Pro Asp Tyr Asp 
          1               5                   10                  15      
          Lys Asn Ala Tyr 
                      20  
          <![CDATA[<210>  74]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  4-Alpha-81]]>
          <![CDATA[<400>  74]]>
          Thr Tyr Pro Asp Tyr Asp Lys Asn Ala Tyr Asp Leu Tyr Gln Asp His 
          1               5                   10                  15      
          Phe Trp Asp Pro 
                      20  
          <![CDATA[<210>  75]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  5-Alpha-91]]>
          <![CDATA[<400>  75]]>
          Asp Leu Tyr Gln Asp His Phe Trp Asp Pro Asp Thr Asp Asn Asn Phe 
          1               5                   10                  15      
          Ser Lys Asp Asn 
                      20  
          <![CDATA[<210>  76]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(10)]]>
          <![CDATA[<223>  6-Alpha-117]]>
          <![CDATA[<400>  76]]>
          Ile Pro Asp Thr Gly Glu Ser Gln Ile Arg 
          1               5                   10  
          <![CDATA[<210>  77]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(10)]]>
          <![CDATA[<223>  7-Alpha-136]]>
          <![CDATA[<400>  77]]>
          Glu Trp Gln Arg Gly Asn Tyr Lys Gln Ala 
          1               5                   10  
          <![CDATA[<210>  78]]>
          <![CDATA[<211>  23]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(23)]]>
          <![CDATA[<223>  8-Alpha-158]]>
          <![CDATA[<400>  78]]>
          Asp Ile Asp Thr Pro Tyr His Pro Ala Asn Val Thr Ala Val Asp Ser 
          1               5                   10                  15      
          Ala Gly His Val Lys Phe Glu 
                      20              
          <![CDATA[<210>  79]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  9-Alpha-170]]>
          <![CDATA[<400>  79]]>
          Val Asp Ser Ala Gly His Val Lys Phe Glu Thr Phe Ala Glu Glu Arg 
          1               5                   10                  15      
          Lys Glu Gln Tyr 
                      20  
          <![CDATA[<210>  80]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)s]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  10-Alpha-181]]>
          <![CDATA[<400>  80]]>
          Thr Phe Ala Glu Glu Arg Lys Glu Gln Tyr Lys Ile Asn Thr Ala Gly 
          1               5                   10                  15      
          Cys Lys Thr Asn 
                      20  
          <![CDATA[<210>  81]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(21)]]>
          <![CDATA[<223>  11-Alpha-191]]>
          <![CDATA[<400>  81]]>
          Lys Ile Asn Thr Val Gly Cys Lys Thr Asn Glu Asp Phe Tyr Ala Asp 
          1               5                   10                  15      
          Ile Leu Lys Asn Lys 
                      20      
          <![CDATA[<210>  82]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  12-Alpha-200]]>
          <![CDATA[<400>  82]]>
          Glu Asp Phe Tyr Ala Asp Ile Leu Lys Asn Lys Asp Phe Asn Ala Trp 
          1               5                   10                  15      
          Ser Lys Glu Tyr 
                      20  
          <![CDATA[<210>  83]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  13-Alpha-210]]>
          <![CDATA[<400>  83]]>
          Lys Asp Phe Asn Ala Trp Ser Lys Glu Tyr Ala Arg Gly Phe Ala Lys 
          1               5                   10                  15      
          Thr Gly Lys Ser 
                      20  
          <![CDATA[<210>  84]]>
          <![CDATA[<211>  17]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(17)]]>
          <![CDATA[<223>  14-Alpha-220]]>
          <![CDATA[<400>  84]]>
          Ala Arg Gly Phe Ala Lys Thr Gly Lys Ser Ile Tyr Tyr Ser His Ala 
          1               5                   10                  15      
          Ser 
          <![CDATA[<210>  85]]>
          <![CDATA[<211>  17]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(17)]]>
          <![CDATA[<223>  15-Alpha-233]]>
          <![CDATA[<400>  85]]>
          Ser His Ala Ser Met Ser His Ser Trp Asp Asp Trp Asp Tyr Ala Ala 
          1               5                   10                  15      
          Lys 
          <![CDATA[<210>  86]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  16-Alpha-240]]>
          <![CDATA[<400>  86]]>
          Ser Trp Asp Asp Trp Asp Tyr Ala Ala Lys Val Thr Leu Ala Asn Ser 
          1               5                   10                  15      
          Gln Lys Gly Thr 
                      20  
          <![CDATA[<210>  87]]>
          <![CDATA[<211>  16]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(16)]]>
          <![CDATA[<223>  17-Alpha-270]]>
          <![CDATA[<400>  87]]>
          Asp Val Ser Glu Gly Asn Asp Pro Ser Val Gly Asn Asn Val Lys Glu 
          1               5                   10                  15      
          <![CDATA[<210>  88]]>
          <![CDATA[<211>  12]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(12)]]>
          <![CDATA[<223>  18-Alpha-291]]>
          <![CDATA[<400>  88]]>
          Ser Thr Ser Gly Glu Lys Asp Ala Gly Thr Asp Asp 
          1               5                   10          
          <![CDATA[<210>  89]]>
          <![CDATA[<211>  13]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(13)]]>
          <![CDATA[<223>  19-Alpha-309]]>
          <![CDATA[<400>  89]]>
          Lys Thr Lys Asp Gly Lys Thr Gln Glu Trp Glu Met Asp 
          1               5                   10              
          <![CDATA[<210>  90]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(21)]]>
          <![CDATA[<223>  20-Alpha-320]]>
          <![CDATA[<400>  90]]>
          Asp Asn Pro Gly Asn Asp Phe Met Ala Gly Ser Lys Asp Thr Tyr Thr 
          1               5                   10                  15      
          Phe Lys Leu Lys Asp 
                      20      
          <![CDATA[<210>  91]]>
          <![CDATA[<211>  20]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(20)]]>
          <![CDATA[<223>  21-Alpha-330]]>
          <![CDATA[<400>  91]]>
          Ser Lys Asp Thr Tyr Thr Phe Lys Leu Lys Asp Glu Asn Leu Lys Ile 
          1               5                   10                  15      
          Asp Asp Ile Gln 
                      20  
          <![CDATA[<210>  92]]>
          <![CDATA[<211>  16]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(16)]]>
          <![CDATA[<223>  22-Alpha-354]]>
          <![CDATA[<400>  92]]>
          Arg Lys Arg Lys Tyr Thr Ala Phe Pro Asp Ala Tyr Lys Pro Glu Asn 
          1               5                   10                  15      
          <![CDATA[<210>  93]]>
          <![CDATA[<211>  19]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  產氣莢膜梭菌 (Clostridium perfringens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(19)]]>
          <![CDATA[<223>  23-Alpha-379]]>
          <![CDATA[<400>  93]]>
          Val Val Asp Lys Asp Ile Asn Glu Trp Ile Ser Gly Asn Ser Thr Tyr 
          1               5                   10                  15      
          Asn Ile Lys 
          <![CDATA[<210>  94]]>
          <![CDATA[<211>  215]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  亞馬遜鸚鵡 (Amazona aestiva)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(215)]]>
          <![CDATA[<223>  高遷移率族蛋白(High mobility group protein) B1]]>
          <![CDATA[<400>  94]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Asp Asp Glu Glu Glu Glu Glu Glu Glu Glu 
                  195                 200                 205             
          Glu Asp Asp Asp Asp Asp Glu 
              210                 215 
          <![CDATA[<210>  95]]>
          <![CDATA[<211>  213]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  波斑鴇 (Chlamydotis macqueenii)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(213)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白(High mobility group protein) B1]]>
          <![CDATA[<400>  95]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Glu Asp Glu Glu Glu Glu Glu Glu Glu Asp 
                  195                 200                 205             
          Glu Asp Asp Asp Asp 
              210             
          <![CDATA[<210>  96]]>
          <![CDATA[<211>  209]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  倉鴞 (Tyto alba)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(209)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白(High mobility group protein)  B1]]>
          <![CDATA[<400>  96]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Asp Asp Glu Glu Glu Glu Glu Glu Glu Asp 
                  195                 200                 205             
          Glu 
          <![CDATA[<210>  97]]>
          <![CDATA[<211>  209]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  冠鸊鷉 (Podiceps cristatus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(209)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白(High mobility group protein)  B1]]>
          <![CDATA[<400>  97]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Asp Glu Glu Glu Glu Glu Glu Glu Asp Glu 
                  195                 200                 205             
          Asp 
          <![CDATA[<210>  98]]>
          <![CDATA[<211>  206]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  煙囪刺尾雨燕 (Chaetura pelagic)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(206)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白質(High mobility group protein)  B1]]>
          <![CDATA[<400>  98]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Asp Asp Glu Glu Glu Glu Glu Glu 
                  195                 200                 205     
          <![CDATA[<210>  99]]>
          <![CDATA[<211>  206]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  紅冠蕉鵑 (Tauraco erythrolphus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(206)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白(High mobility group protein)  B1]]>
          <![CDATA[<400>  99]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Glu Glu Glu Asp Glu Asp Asp Glu Glu Glu Glu Glu Glu 
                  195                 200                 205     
          <![CDATA[<210>  100]]>
          <![CDATA[<211>  203]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  白尾鸏 (Phaethon lepturus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(203)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白(High mobility group protein) B1]]>
          <![CDATA[<400>  100]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Asp Asp Glu Glu Glu 
                  195                 200             
          <![CDATA[<210>  101]]>
          <![CDATA[<211>  201]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  黃喉沙雞 (Pterocles gutturalis)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(201)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白(High mobility group protein) B1]]>
          <![CDATA[<400>  101]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Thr Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Asp Asp Glu 
                  195                 200     
          <![CDATA[<210>  102]]>
          <![CDATA[<211>  200]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  紅喉潛鳥 (Gavia stellate)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(200)]]>
          <![CDATA[<223>  部分的高遷移率族蛋白(High mobility group protein) B1]]>
          <![CDATA[<400>  102]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ser Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Leu Arg Tyr Glu Lys Glu Met Lys Asn Tyr Val Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Phe Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Val Asp Ala Gly Lys Lys Val Val Ala 
                          165                 170                 175     
          Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Asp 
                      180                 185                 190         
          Glu Asp Glu Glu Asp Glu Asp Glu 
                  195                 200 
          <![CDATA[<210>  103]]>
          <![CDATA[<211>  176]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  鼴鼠(Nannospalax ehrenbergi)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(176)]]>
          <![CDATA[<223>  高遷移率族蛋白(High mobility group protein)]]>
          <![CDATA[<400>  103]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Glu Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          <![CDATA[<210>  104]]>
          <![CDATA[<211>  176]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  多疣壁虎(Gekko japonicas)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(176)]]>
          <![CDATA[<223>  高遷移率族蛋白(High mobility group protein) B1]]>
          <![CDATA[<400>  104]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Glu Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val 
                          165                 170                 175     
          <![CDATA[<210>  105]]>
          <![CDATA[<211>  175]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  樹鼩 (Tupaia chinensis)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(175)]]>
          <![CDATA[<223>  高遷移率族蛋白質(High mobility group protein) B1]]>
          <![CDATA[<400>  105]]>
          Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr 
          1               5                   10                  15      
          Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro 
                      20                  25                  30          
          Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg 
                  35                  40                  45              
          Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala 
              50                  55                  60                  
          Lys Ala Asp Lys Ala His Tyr Glu Arg Glu Met Lys Thr Phe Ile Pro 
          65                  70                  75                  80  
          Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys 
                          85                  90                  95      
          Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys 
                      100                 105                 110         
          Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys 
                  115                 120                 125             
          Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr 
              130                 135                 140                 
          Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala 
          145                 150                 155                 160 
          Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ser Lys Lys Gly Val 
                          165                 170                 175 
          <![CDATA[<210>  106]]>
          <![CDATA[<211>  272]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(272)]]>
          <![CDATA[<223>  雞的CD154 (原雞(Gallus gallus))]]>
          <![CDATA[<400>  106]]>
          Met Asn Glu Ala Tyr Ser Pro Ala Ala Pro Arg Pro Met Gly Ser Thr 
          1               5                   10                  15      
          Ser Pro Ser Thr Met Lys Met Phe Met Cys Phe Leu Ser Val Phe Met 
                      20                  25                  30          
          Val Val Gln Thr Ile Gly Thr Val Leu Phe Cys Leu Tyr Leu His Met 
                  35                  40                  45              
          Lys Met Asp Lys Met Glu Glu Val Leu Ser Leu Asn Glu Asp Tyr Ile 
              50                  55                  60                  
          Phe Leu Arg Lys Val Gln Lys Cys Gln Thr Gly Glu Asp Gln Lys Ser 
          65                  70                  75                  80  
          Thr Leu Leu Asp Cys Glu Lys Val Leu Lys Gly Phe Gln Asp Leu Gln 
                          85                  90                  95      
          Cys Lys Asp Arg Thr Ala Ser Glu Glu Leu Pro Lys Phe Glu Met His 
                      100                 105                 110         
          Arg Gly His Glu His Pro His Leu Lys Ser Arg Asn Glu Thr Ser Val 
                  115                 120                 125             
          Ala Glu Glu Lys Arg Gln Pro Ile Ala Thr His Leu Ala Gly Val Lys 
              130                 135                 140                 
          Ser Asn Thr Thr Val Arg Val Leu Lys Trp Met Thr Thr Ser Tyr Ala 
          145                 150                 155                 160 
          Pro Thr Ser Ser Leu Ile Ser Tyr His Glu Gly Lys Leu Lys Val Glu 
                          165                 170                 175     
          Lys Ala Gly Leu Tyr Tyr Ile Tyr Ser Gln Val Ser Phe Cys Thr Lys 
                      180                 185                 190         
          Ala Ala Ala Ser Ala Pro Phe Thr Leu Tyr Ile Tyr Leu Tyr Leu Pro 
                  195                 200                 205             
          Met Glu Glu Asp Arg Leu Leu Met Lys Gly Leu Asp Thr His Ser Thr 
              210                 215                 220                 
          Ser Thr Ala Leu Cys Glu Leu Gln Ser Ile Arg Glu Gly Gly Val Phe 
          225                 230                 235                 240 
          Glu Leu Arg Gln Gly Asp Met Val Phe Val Asn Val Thr Asp Ser Thr 
                          245                 250                 255     
          Ala Val Asn Val Asn Pro Gly Asn Thr Tyr Phe Gly Met Phe Lys Leu 
                      260                 265                 270         
          <![CDATA[<210>  107]]>
          <![CDATA[<211>  261]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  智人(Homo sapiens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(261)]]>
          <![CDATA[<223>  人的CD154  智人(Homo sapiens)]]>
          <![CDATA[<400>  107]]>
          Met Ile Glu Thr Tyr Asn Gln Thr Ser Pro Arg Ser Ala Ala Thr Gly 
          1               5                   10                  15      
          Leu Pro Ile Ser Met Lys Ile Phe Met Tyr Leu Leu Thr Val Phe Leu 
                      20                  25                  30          
          Ile Thr Gln Met Ile Gly Ser Ala Leu Phe Ala Val Tyr Leu His Arg 
                  35                  40                  45              
          Arg Leu Asp Lys Ile Glu Asp Glu Arg Asn Leu His Glu Asp Phe Val 
              50                  55                  60                  
          Phe Met Lys Thr Ile Gln Arg Cys Asn Thr Gly Glu Arg Ser Leu Ser 
          65                  70                  75                  80  
          Leu Leu Asn Cys Glu Glu Ile Lys Ser Gln Phe Glu Gly Phe Val Lys 
                          85                  90                  95      
          Asp Ile Met Leu Asn Lys Glu Glu Thr Lys Lys Glu Asn Ser Phe Glu 
                      100                 105                 110         
          Met Gln Lys Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser 
                  115                 120                 125             
          Glu Ala Ser Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly 
              130                 135                 140                 
          Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln 
          145                 150                 155                 160 
          Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr 
                          165                 170                 175     
          Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser 
                      180                 185                 190         
          Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala 
                  195                 200                 205             
          Ala Asn Thr His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His 
              210                 215                 220                 
          Leu Gly Gly Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn 
          225                 230                 235                 240 
          Val Thr Asp Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe 
                          245                 250                 255     
          Gly Leu Leu Lys Leu 
                      260     
          <![CDATA[<210>  108]]>
          <![CDATA[<211>  11]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  智人(Homo sapiens)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(11)]]>
          <![CDATA[<223>  部分的人的CD154  智人(Homo sapiens)]]>
          <![CDATA[<400>  108]]>
          Trp Ala Glu Lys Gly Tyr Tyr Thr Met Ser Cys 
          1               5                   10      
          <![CDATA[<210>  109]]>
          <![CDATA[<211>  11]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  原雞(Gallus gallus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(11)]]>
          <![CDATA[<223>  雞的 CD154胜肽  原雞(Gallus gallus)]]>
          <![CDATA[<400>  109]]>
          Trp Met Thr Thr Ser Tyr Ala Pro Thr Ser Ser 
          1               5                   10      
          <![CDATA[<210>  110]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  鴨屬 (Anas sp.)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(10)]]>
          <![CDATA[<223>  鴨的 CD154胜肽  鴨屬 (Anas sp.)]]>
          <![CDATA[<400>  110]]>
          Trp Asn Lys Thr Ser Tyr Ala Pro Met Asn 
          1               5                   10  
          <![CDATA[<210>  111]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  小鼠屬 (Mus sp.)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(10)]]>
          <![CDATA[<223>  小鼠的CD154胜肽 小鼠屬 (Mus p.)]]>
          <![CDATA[<400>  111]]>
          Trp Ala Lys Lys Gly Tyr Tyr Thr Met Lys 
          1               5                   10  
          <![CDATA[<210>  112]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  家牛 (Bos Taurus)]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  misc_feature]]>
          <![CDATA[<222>  (1)..(10)]]>
          <![CDATA[<223>  牛的CD154胜肽 家牛(Bos taurus)]]>
          <![CDATA[<400>  112]]>
          Trp Ala Pro Lys Gly Tyr Tyr Thr Leu Ser 
          1               5                   10  
          <![CDATA[<210>  113]]>
          <![CDATA[<211>  139]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：重鏈( Heavy chain)，領先股( Leader) ]]>
                 序列(sequence)-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4
          <![CDATA[<400>  113]]>
          Met Ala Val Leu Ala Leu Leu Leu Cys Leu Val Ala Phe Pro Ser Cys 
          1               5                   10                  15      
          Thr Leu Ser Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala 
                      20                  25                  30          
          Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu 
                  35                  40                  45              
          Thr Thr Tyr Asp Ile Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 
              50                  55                  60                  
          Glu Trp Leu Gly Ile Ile Trp Thr Gly Gly Gly Thr Asn Tyr Asn Ser 
          65                  70                  75                  80  
          Ala Phe Met Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln 
                          85                  90                  95      
          Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr 
                      100                 105                 110         
          Tyr Cys Val Arg Asp Arg Gly Tyr Tyr Val Tyr Tyr Ser Met Asp Tyr 
                  115                 120                 125             
          Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser 
              130                 135                 
          <![CDATA[<210>  114]]>
          <![CDATA[<211>  127]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：輕鏈 (Light chain)，領先股 (Leader) ]]>
                 序列(sequence)-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4
          <![CDATA[<400>  114]]>
          Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln 
          1               5                   10                  15      
          Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser 
                      20                  25                  30          
          Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp 
                  35                  40                  45              
          Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val 
              50                  55                  60                  
          Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser 
          65                  70                  75                  80  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser 
                          85                  90                  95      
          Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn 
                      100                 105                 110         
          Met Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                  115                 120                 125         
          <![CDATA[<210>  115]]>
          <![CDATA[<211>  264]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：胺基酸]]>
          <![CDATA[<400>  115]]>
          Met Thr Gln Ser Gln Lys Phe Met Ser Thr Ser Val Gly Asp Arg Val 
          1               5                   10                  15      
          Ser Val Thr Cys Lys Ala Ser Gln Asn Val Gly Thr Asn Val Ala Trp 
                      20                  25                  30          
          Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile Tyr Ser Ala 
                  35                  40                  45              
          Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser 
              50                  55                  60                  
          Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Val Gln Ser Glu Asp Leu 
          65                  70                  75                  80  
          Ala Asp Tyr Phe Cys Gln Gln Tyr Ser Ser Tyr Pro Leu Thr Phe Gly 
                          85                  90                  95      
          Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Ser Ser Arg Ser Ser Leu 
                      100                 105                 110         
          Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Thr 
                  115                 120                 125             
          Ser Val Arg Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
              130                 135                 140                 
          Tyr Ile Tyr Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
          145                 150                 155                 160 
          Gly Trp Ile Tyr Pro Gly Asn Val Asn Thr Lys Tyr Asn Glu Lys Phe 
                          165                 170                 175     
          Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
                      180                 185                 190         
          Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                  195                 200                 205             
          Ala Arg Arg Gly Thr Gly Thr Val Val Phe Asp Tyr Trp Gly His Gly 
              210                 215                 220                 
          Thr Thr Leu Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Thr 
          225                 230                 235                 240 
          Ser Gly Gln Ala Gly Gln His His His His His His Gly Ala Tyr Pro 
                          245                 250                 255     
          Tyr Asp Val Pro Asp Tyr Ala Ser 
                      260                 
          <![CDATA[<210>  116]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：重鏈(Heavy chain) CDR1]]>
          <![CDATA[<400>  116]]>
          Gly Phe Ser Leu Thr Thr Tyr Asp Ile Asn 
          1               5                   10  
          <![CDATA[<210>  117]]>
          <![CDATA[<211>  16]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：重鏈( Heavy chain) CDR2]]>
          <![CDATA[<400>  117]]>
          Ile Ile Trp Thr Gly Gly Gly Thr Asn Tyr Asn Ser Ala Phe Met Ser 
          1               5                   10                  15      
          <![CDATA[<210>  118]]>
          <![CDATA[<211>  12]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：重鏈( Heavy chain) CDR3]]>
          <![CDATA[<400>  118]]>
          Asp Arg Gly Tyr Tyr Val Tyr Tyr Ser Met Asp Tyr 
          1               5                   10          
          <![CDATA[<210>  119]]>
          <![CDATA[<211>  11]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：輕鏈( Light chain) CDR1]]>
          <![CDATA[<400>  119]]>
          Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn 
          1               5                   10      
          <![CDATA[<210>  120]]>
          <![CDATA[<211>  7]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：輕鏈(Light chain) CDR2]]>
          <![CDATA[<400>  120]]>
          Tyr Thr Ser Arg Leu His Ser 
          1               5           
          <![CDATA[<210>  121]]>
          <![CDATA[<211>  9]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：輕鏈 (Light chain) CDR3]]>
          <![CDATA[<400>  121]]>
          Gln Gln Gly Asn Met Phe Pro Trp Thr 
          1               5                   
          <![CDATA[<210>  122]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：VH，CDR1]]>
          <![CDATA[<400>  122]]>
          Asn Tyr Tyr Ile Tyr 
          1               5   
          <![CDATA[<210>  123]]>
          <![CDATA[<211>  17]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：VH，CDR2]]>
          <![CDATA[<400>  123]]>
          Trp Ile Tyr Pro Gly Asn Val Asn Thr Lys Tyr Asn Glu Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210>  124]]>
          <![CDATA[<211>  11]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：VH，CDR3]]>
          <![CDATA[<400>  124]]>
          Arg Gly Thr Gly Thr Val Val Phe Asp Tyr Trp 
          1               5                   10      
          <![CDATA[<210>  125]]>
          <![CDATA[<211>  11]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：VL，CDR1]]>
          <![CDATA[<400>  125]]>
          Lys Ala Ser Gln Asn Val Gly Thr Asn Val Ala 
          1               5                   10      
          <![CDATA[<210>  126]]>
          <![CDATA[<211>  7]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：VL，CDR2]]>
          <![CDATA[<400>  126]]>
          Ser Ala Ser Tyr Arg Tyr Ser 
          1               5           
          <![CDATA[<210>  127]]>
          <![CDATA[<211>  9]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的，VL，CDR3]]>
          <![CDATA[<400>  127]]>
          Gln Gln Tyr Ser Ser Tyr Pro Leu Thr 
          1               5                   
          <![CDATA[<210>  128]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  DNA]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：AOXSeqF]]>
          <![CDATA[<400>  128]]>
          gactggttcc aattgacaag c                                                 21
          <![CDATA[<210>  129]]>
          <![CDATA[<211>  21]]>
          <![CDATA[<212>  DNA]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  合成的：AOXSeqR]]>
          <![CDATA[<400>  129]]>
          gcaaatggca ttctgacatc c                                                 21
Figure 12_A0101_SEQ_0001
Figure 12_A0101_SEQ_0002
Figure 12_A0101_SEQ_0003
Figure 12_A0101_SEQ_0004
Figure 12_A0101_SEQ_0005
Figure 12_A0101_SEQ_0006
Figure 12_A0101_SEQ_0007
Figure 12_A0101_SEQ_0008
Figure 12_A0101_SEQ_0009
Figure 12_A0101_SEQ_0010
Figure 12_A0101_SEQ_0011
Figure 12_A0101_SEQ_0012
Figure 12_A0101_SEQ_0013
Figure 12_A0101_SEQ_0014
Figure 12_A0101_SEQ_0015
Figure 12_A0101_SEQ_0016
Figure 12_A0101_SEQ_0017
Figure 12_A0101_SEQ_0018
Figure 12_A0101_SEQ_0019
Figure 12_A0101_SEQ_0020
Figure 12_A0101_SEQ_0021
Figure 12_A0101_SEQ_0022
Figure 12_A0101_SEQ_0023
Figure 12_A0101_SEQ_0024
Figure 12_A0101_SEQ_0025
Figure 12_A0101_SEQ_0026
Figure 12_A0101_SEQ_0027
Figure 12_A0101_SEQ_0028
Figure 12_A0101_SEQ_0029
Figure 12_A0101_SEQ_0030
Figure 12_A0101_SEQ_0031
Figure 12_A0101_SEQ_0032
Figure 12_A0101_SEQ_0033
Figure 12_A0101_SEQ_0034
Figure 12_A0101_SEQ_0035
Figure 12_A0101_SEQ_0036
Figure 12_A0101_SEQ_0037
Figure 12_A0101_SEQ_0038
Figure 12_A0101_SEQ_0039
Figure 12_A0101_SEQ_0040
Figure 12_A0101_SEQ_0041
Figure 12_A0101_SEQ_0042
Figure 12_A0101_SEQ_0043
Figure 12_A0101_SEQ_0044
Figure 12_A0101_SEQ_0045
Figure 12_A0101_SEQ_0046
Figure 12_A0101_SEQ_0047
Figure 12_A0101_SEQ_0048
Figure 12_A0101_SEQ_0049
Figure 12_A0101_SEQ_0050
Figure 12_A0101_SEQ_0051
Figure 12_A0101_SEQ_0052
Figure 12_A0101_SEQ_0053
Figure 12_A0101_SEQ_0054
Figure 12_A0101_SEQ_0055
Figure 12_A0101_SEQ_0056
Figure 12_A0101_SEQ_0057
Figure 12_A0101_SEQ_0058
Figure 12_A0101_SEQ_0059
Figure 12_A0101_SEQ_0060
Figure 12_A0101_SEQ_0061
Figure 12_A0101_SEQ_0062
Figure 12_A0101_SEQ_0063
Figure 12_A0101_SEQ_0064
Figure 12_A0101_SEQ_0065
Figure 12_A0101_SEQ_0066
Figure 12_A0101_SEQ_0067
Figure 12_A0101_SEQ_0068
Figure 12_A0101_SEQ_0069
Figure 12_A0101_SEQ_0070
Figure 12_A0101_SEQ_0071
Figure 12_A0101_SEQ_0072
Figure 12_A0101_SEQ_0073
Figure 12_A0101_SEQ_0074
Figure 12_A0101_SEQ_0075
Figure 12_A0101_SEQ_0076
Figure 12_A0101_SEQ_0077
Figure 12_A0101_SEQ_0078
Figure 12_A0101_SEQ_0079
Figure 12_A0101_SEQ_0080
Figure 12_A0101_SEQ_0081
Figure 12_A0101_SEQ_0082
Figure 12_A0101_SEQ_0083
Figure 12_A0101_SEQ_0084
Figure 12_A0101_SEQ_0085
Figure 12_A0101_SEQ_0086
Figure 12_A0101_SEQ_0087
Figure 12_A0101_SEQ_0088
Figure 12_A0101_SEQ_0089
Figure 12_A0101_SEQ_0090
Figure 12_A0101_SEQ_0091
Figure 12_A0101_SEQ_0092
Figure 12_A0101_SEQ_0093
無。

Claims (28)

  1. 一種酵母菌疫苗組合物，其包含： 一酵母菌，其包含編碼為一HMGB1多肽或一CD40配位體的一免疫刺激性多核苷酸， 其中，該酵母菌表達該HMGB1多肽或該CD40配位體於該酵母菌的表面。
  2. 如請求項1所述之疫苗組合物，其更包含編碼一抗原性多肽的一抗原多核苷酸。
  3. 如請求項2所述之疫苗組合物，其中該酵母菌表達該抗原性多肽於該酵母菌的表面上。
  4. 如請求項2所述之疫苗組合物，其中該抗原性多肽係選自由流行性感冒多肽、彎曲桿菌多肽、梭菌多肽、沙門氏菌多肽、艾美球蟲多肽與腫瘤相關多肽所組成的群組。
  5. 如請求項4所述之疫苗組合物，其中該抗原性多肽係選自SEQ ID NO：39至93中的任意。
  6. 如請求項2所述之疫苗組合物，其中該酵母菌包含多於一種的抗原性多核苷酸。
  7. 如請求項6所述之疫苗組合物，其中該多於一種的抗原性多核苷酸衍生自一種以上的物種。
  8. 如請求項1所述之疫苗組合物，其中該酵母菌係為畢赤酵母菌。
  9. 如請求項8所述之疫苗組合物，其中該畢赤酵母菌係為巴斯德畢赤酵母菌。
  10. 如請求項1所述之疫苗組合物，其中該HMGB1多肽係為全長HMGB1多肽。
  11. 如請求項10所述之疫苗組合物，其中該HMGB1多肽係選自由SEQ ID NO：2至23與SEQ ID NO：94至105中提供的HMGB1序列以及與SEQ ID NO：2至23與SEQ ID NO：94至105序列具有95%相同性的序列所組成的群組。
  12. 如請求項1所述之疫苗組合物，其中該CD40配位體係選自CD154多肽與CD40激動性抗體或其部分。
  13. 如請求項1所述之疫苗組合物，其中該CD40配位體包含SEQ ID NO：106至127中的至少一。
  14. 如請求項2所述之疫苗組合物，其中該抗原性多肽與該HMGB1多肽或CD40配位體係為一融合蛋白的部分。
  15. 如請求項1所述之疫苗組合物，其中該HMGB1多肽或該CD40配位體係為GPI錨定。
  16. 如請求項15所述之疫苗組合物，其中該免疫刺激性多核苷酸被插入至編碼來自啤酒酵母菌的α凝集素的多核苷酸中。
  17. 如請求項1所述之疫苗組合物，其中該免疫刺激性多核苷酸更包含編碼至少兩個連結子胺基酸的連結子寡核苷酸。
  18. 一種醫藥組合物，其包含如請求項1所述之疫苗組合物及一藥學上可接受之載體。
  19. 如請求項18所述之醫藥組合物，其中該藥學上可接受之載體對於接受口服或是鼻內施用為可接受的。
  20. 如請求項18所述之醫藥組合物，其中該酵母菌不能複製。
  21. 如請求項18所述之醫藥組合物，其中該酵母菌係為失活或是死亡。
  22. 一種請求項1所述之疫苗組合物在一藥劑中用以增強受試者對於該疫苗組合物的免疫反應的用途。
  23. 如請求項22所述之用途，其中該疫苗組合物係為經口或鼻內施用。
  24. 如請求項22所述之用途，其中該受試者自係選自由人類、牛、貓、狗、豬、魚、鯰魚、鯛魚、金魚、鳥、家禽、雞與火雞所組成的群組。
  25. 如請求項22所述之用途，其中於施用該疫苗組合物後，增強對於該疫苗組合物或該疫苗組合物中的多肽的抗體反應。
  26. 如請求項25所述之用途，其中該免疫反應係為IgA抗體反應。
  27. 如請求項22所述之用途，其中在該疫苗組合物中的該酵母菌不能於該受試者中複製。
  28. 如請求項22所述之用途，其中於施用至該受試者前，該疫苗組合物中的該酵母菌係為失活或是死亡。
TW111105339A 2016-05-03 2017-05-03 包含免疫刺激性及抗原性多肽的酵母菌疫苗載體以及其使用方法 TWI843057B (zh)

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