CN110646612A - 一种用于检测血清hpv抗体的试剂及试剂盒 - Google Patents
一种用于检测血清hpv抗体的试剂及试剂盒 Download PDFInfo
- Publication number
- CN110646612A CN110646612A CN201910941601.5A CN201910941601A CN110646612A CN 110646612 A CN110646612 A CN 110646612A CN 201910941601 A CN201910941601 A CN 201910941601A CN 110646612 A CN110646612 A CN 110646612A
- Authority
- CN
- China
- Prior art keywords
- hpv
- kit
- reagent
- detecting serum
- vlps
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 210000002966 serum Anatomy 0.000 title claims abstract description 24
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 13
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 7
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 19
- 230000000903 blocking effect Effects 0.000 claims description 8
- 239000011248 coating agent Substances 0.000 claims description 5
- 238000000576 coating method Methods 0.000 claims description 5
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 claims description 5
- 238000008157 ELISA kit Methods 0.000 claims description 2
- 239000007853 buffer solution Substances 0.000 claims description 2
- 239000003550 marker Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 235000020183 skimmed milk Nutrition 0.000 claims description 2
- 241000701806 Human papillomavirus Species 0.000 description 42
- 206010008342 Cervix carcinoma Diseases 0.000 description 8
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 8
- 201000010881 cervical cancer Diseases 0.000 description 8
- 229960002566 papillomavirus vaccine Drugs 0.000 description 8
- 229960005486 vaccine Drugs 0.000 description 8
- 238000002255 vaccination Methods 0.000 description 7
- 241000341655 Human papillomavirus type 16 Species 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000009608 Papillomavirus Infections Diseases 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000032271 Malignant tumor of penis Diseases 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 241001409305 Siraitia Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003627 allelochemical Substances 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229940031416 bivalent vaccine Drugs 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000000797 effect on infection Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940031348 multivalent vaccine Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 229940031351 tetravalent vaccine Drugs 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/20011—Papillomaviridae
- C12N2710/20023—Virus like particles [VLP]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/01—DNA viruses
- G01N2333/025—Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2469/00—Immunoassays for the detection of microorganisms
- G01N2469/20—Detection of antibodies in sample from host which are directed against antigens from microorganisms
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明涉及一种用于检测血清HPV抗体的试剂，包含HPV6、11、16、18、31、33、45、52和58九种亚型的VLP，其中每种HVP亚型的VLP均由该亚型的L1蛋白和L2蛋白包装而成。还涉及一种包括上述试剂的试剂盒。
Description
技术领域
本发明涉及HPV防治领域，更特别地，涉及一种用于检测血清HPV抗体的试剂及试剂盒。
背景技术
宫颈癌是全球女性第二大癌症，仅次于乳腺癌。近年来，我国宫颈癌发病率持续走高，平均每年以8.7％的速度增长，其中农村地区增长率为10.3％，城市地区增长为5.6％；而死亡率则以8.1％的速度增长，防治形式不容乐观。宫颈癌的元凶是人乳头瘤病毒(HumanPapillomavirus,HPV)持续感染。根据HPV致病性的不同，将其分为低危型HPV和高危型HPV；低危型(HPV6、 11型等)，可导致生殖器官的疣和良性肿瘤；高危型HPV(HPV16、18、31、 33、45、52、58型等)会导致女性宫颈癌、男性阴茎癌。其中，约54％的宫颈癌是HPV16感染引起的，约16％的宫颈癌是HPV18感染引起的，因此控制高危型HPV病毒的持续感染对宫颈癌的防治有非常大的意义，目前主要的防控方式是通过大力推广HPV筛查和接种HPV疫苗。目前市场上已有的HPV疫苗是葛兰素史克(GSK)公司针对HPV16和HPV18的希瑞适双价疫苗和默沙东公司的针对HPV16,HPV18,HPV11和HPV6的佳达修四价疫苗以及针对HPV(6、 11、16、18、31、33、45、52、58型)的佳达修九价疫苗。这些疫苗是利用不同表达系统来生产HPVL1蛋白的病毒样颗粒(Viral likeparticle，VLP)，通过接种HPV VLP从而在机体内产生高效的保护性抗体来抑制病毒感染。因此是否产生了高效的保护性抗体是衡量HPV疫苗接种成功的重要指标。
研究表明，不同亚型的HPV VLP诱导的抗体主要抑制自身型别HPV病毒的感染，针对其它型别HPV感染的交叉抑制效果不强。由于不同个体对疫苗的免疫反应是有差别的，产生相应保护抗体的水平也不同，多价疫苗中不同型VLP的抗原性也有差异，因此随着HPV疫苗的广泛接种，有必要检测HPV 疫苗是否接种成功。研究表明当病毒样颗粒诱导的抗血清效价达到1000倍的血清稀释时，才会有针对HPV感染的很好的保护效果。另外最近爆发HPV假疫苗事件，以及存在HPV疫苗运输和保存过程中导致疫苗失效或者单人份 HPV疫苗的接种剂量接种了多个受试者等原因导致HPV疫苗接种后未能产生高滴度的保护性抗体。
鉴于此，评价HPV疫苗接种后是否产生了高滴度的保护性抗体显得十分必要。
发明内容
为解决以上问题，本发明提供了一种用于检测血清HPV抗体的试剂，其特征在于，包含HPV6、11、16、18、31、33、45、52和58九种亚型的VLP，其中每种HVP亚型的VLP均由该亚型的L1蛋白和L2蛋白包装而成。
在一个优选实施方案中，所述九种亚型的VLP溶于pH 8.5-10的CBS缓冲溶液中。
在一个优选实施方案中，所述每种HVP亚型的VLP的浓度为60-150 ng/mL。
本发明还提供了一种用于检测血清HPV抗体的试剂盒，包括上述用于检测血清HPV抗体的试剂。
在一个优选实施方案中，所述试剂盒为ELISA试剂盒，所述用于检测血清HPV抗体的试剂作为包被液。
在一个优选实施方案中，所述试剂盒还包括封闭液。
在一个优选实施方案中，所述封闭液为含有3-10g/100mL的脱脂奶粉的PBST溶液。
在一个优选实施方案中，所述试剂盒还包括人二抗，所述人二抗具有可识别的标志物。
附图说明
图1为HPV疫苗接种者针对HPV VLP效价测定。PV4001,PV4002和 PV4003为接种HPV4价疫苗的受试者血清，PV9004为接种HPV9价疫苗受试者血清，H001,002,003为未接种HPV疫苗受试者血清，作为阴性对照。
图2 HPV疫苗接种者针对不同亚型HPV VLP效价测定。PV4001,PV4002 和PV4003为接种HPV4价疫苗的受试者血清，PV9004为接种HPV9价疫苗受试者血清，H001,002,003为未接种HPV疫苗受试者血清，作为阴性对照。 1:500，1:1000，1:10000代表血清稀释倍数。
具体实施方式
1.制备HPV VLP
从NCBI网站上获取HPV6、11、16、18、31、33、45、52、58九个亚型 HPV病毒的L1,L2序列，将序列克隆到pCDNA3.1。以CMV为启动子，L1和 L2两个ORF框之间通过IRES连接。将构建正确的克隆，摇菌，无内毒素质粒大提备用。
将上述构建好的质粒转染293T细胞，44-52h后，裂解细胞，加入pH9.0 的硫酸铵溶液涡旋后，放入37℃温箱中成熟过夜，通过盐粗提赫超速离心纯化获得高纯度的不同亚型的HPV VLP蛋白。
2.HPV抗体检测剂
将以上9种VLP等比例混合，然后按照总浓度900ng/ml将9种亚型的 VLP等比例混合，随后按照总浓度900ng/ml稀释到CBS包被液中、100ul/ 孔，即每种VLP10ng/孔包被在ELISA板条中，4℃孵育过夜。次日，以洗涤缓冲液PBST洗涤3遍，250ul PBST/孔，甩干孔中洗涤液并于无尘吸水纸上拍干。封闭：配制含有5％牛血清的PBST作为封闭液，加封闭液于酶标板中， 250ul/孔，置于37℃2小时，封闭完毕洗涤3遍。上样：将疫苗接种者血清样品及健康志愿者血清样品以1:900开始，作3倍稀释在封闭液中，共11 个梯度，每个梯度100ul/孔上样，37℃1.5小时，上样完毕洗涤3遍。二抗：将羊抗人-HRP二抗以1：5000稀释在封闭液中，100ul/孔加入酶标板中，置于4℃45min，二抗孵育完毕洗涤4遍。显色：将显色底物液TMB A液和B 液按照1:1混匀，100ul/孔加入酶标板中，37℃10min。终止：向显色完毕的孔中加终止液1M H2SO4，50ul/孔。读数：于酶标仪上波长450nm处读取 OD值，并保存数据。结果如图1所示：四位HPV疫苗接种者(PV4001,PV4002, PV4003和PV9004)血清里，PV4003和PV9004产生了高滴度针对HPV VLP 的抗血清，PV4003的血清效价为729,000倍稀释，PV9004的血清效价为 243,000倍稀释。而其他的疫苗接种者以未接种疫苗的受试者(H001,H002 和H003)体内均未观察到高滴度针对HPVVLP的抗血清。以上结果提示，部分HPV疫苗接种者体内产生了高滴度针对HPVVLP的抗血清，然而部分受试者接种疫苗后并未成功得产生针对HPV VLP的高滴度抗体。
由于不同亚型的VLP蛋白诱导产生的抗体大多只抑制自身型别的HPV感染，另外HPV16和HPV18会诱发80％的宫颈癌，因此检测接种疫苗后是否产生了针对不同型别的高滴度的抗体，尤其是针对HPV16和HPV18高滴度的抗体显得十分必要。
包被：将不同亚型的VLP以100ng/ml稀释到CBS包被液中，100ul/孔，即10ng/孔加入ELISA板条中，4℃孵育过夜。封闭同前。上样：将疫苗接种者血清样品及健康志愿者血清样品以1:500，1:1000，1:5000开始三个稀释在封闭液中，100ul/孔，37度1.5h。其余同前。结果如图2所示，PV4001 受试者血清内只含有针对HPV18和HPV33的高滴度抗血清，PV4003受试者接种的4价的HPV疫苗，成功的产生了针对四个亚型HPV6，11，16和18的特异性抗体，另外还交叉结合HPV33；另外接种9价疫苗的受试者PV9004 成功的产生了针对8个亚型HPV6,11,18,31,33,45,52,58的特异性高滴度抗体，但是没能检测到针对高危亚型HPV16的特异性抗体。由此可见，虽然 PV9004疫苗接种者体内产生了高滴度的HPV VLP抗体，但是未能成功产生针对高危亚型HPV16的高滴度抗体。
以上所述仅为本发明的较佳实施例，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (8)
1.一种用于检测血清HPV抗体的试剂，其特征在于，包含HPV6、11、16、18、31、33、45、52和58九种亚型的VLP，其中每种HVP亚型的VLP均由该亚型的L1蛋白和L2蛋白包装而成。
2.根据权利要求1所述的用于检测血清HPV抗体的试剂，其特征在于，所述九种亚型的VLP溶于pH 8.5-10的CBS缓冲溶液中。
3.根据权利要求2所述的用于检测血清HPV抗体的试剂，其特征在于，所述每种HVP亚型的VLP的浓度为60-150ng/mL。
4.一种用于检测血清HPV抗体的试剂盒，其特征在于，包括权利要求1-3中任一项所述的用于检测血清HPV抗体的试剂。
5.根据权利要求4所述的试剂盒，其特征在于，所述试剂盒为ELISA试剂盒，所述用于检测血清HPV抗体的试剂作为包被液。
6.根据权利要求5所述的试剂盒，其特征在于，还包括封闭液。
7.根据权利要求6所述的试剂盒，其特征在于，所述封闭液为含有3-10g/100mL的脱脂奶粉的PBST溶液。
8.根据权利要求5所述的试剂盒，其特征在于，还包括人二抗，所述人二抗具有可识别的标志物。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910941601.5A CN110646612A (zh) | 2019-09-30 | 2019-09-30 | 一种用于检测血清hpv抗体的试剂及试剂盒 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910941601.5A CN110646612A (zh) | 2019-09-30 | 2019-09-30 | 一种用于检测血清hpv抗体的试剂及试剂盒 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110646612A true CN110646612A (zh) | 2020-01-03 |
Family
ID=68993414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910941601.5A Pending CN110646612A (zh) | 2019-09-30 | 2019-09-30 | 一种用于检测血清hpv抗体的试剂及试剂盒 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110646612A (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1498963A (zh) * | 2002-11-08 | 2004-05-26 | 中国医学科学院基础医学研究所 | 人乳头瘤病毒的病毒样颗粒的生产方法 |
| US20040224305A1 (en) * | 2000-06-21 | 2004-11-11 | Wilson Susan D. | Chimeric human papillomavirus (HPV) L1 molecules and uses therefor |
| US20120171290A1 (en) * | 2009-04-13 | 2012-07-05 | Coursaget Pierre L | Hpv particles and uses thereof |
| CN103483446A (zh) * | 2012-06-08 | 2014-01-01 | 厦门大学 | 抗hpv l2 蛋白的广谱中和单克隆抗体或其抗原结合片段及它们的用途 |
| CN105367652A (zh) * | 2015-07-23 | 2016-03-02 | 北京生物制品研究所有限责任公司 | 一种抗hpv16l1蛋白的单克隆抗体、其制备方法和应用 |
| CN107080833A (zh) * | 2009-04-10 | 2017-08-22 | 约翰·霍普金斯大学 | 作为广谱人类乳头状瘤病毒（hpv）疫苗的乳头状瘤病毒样颗粒（vlp） |
-
2019
- 2019-09-30 CN CN201910941601.5A patent/CN110646612A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040224305A1 (en) * | 2000-06-21 | 2004-11-11 | Wilson Susan D. | Chimeric human papillomavirus (HPV) L1 molecules and uses therefor |
| CN1498963A (zh) * | 2002-11-08 | 2004-05-26 | 中国医学科学院基础医学研究所 | 人乳头瘤病毒的病毒样颗粒的生产方法 |
| CN107080833A (zh) * | 2009-04-10 | 2017-08-22 | 约翰·霍普金斯大学 | 作为广谱人类乳头状瘤病毒（hpv）疫苗的乳头状瘤病毒样颗粒（vlp） |
| US20120171290A1 (en) * | 2009-04-13 | 2012-07-05 | Coursaget Pierre L | Hpv particles and uses thereof |
| CN103483446A (zh) * | 2012-06-08 | 2014-01-01 | 厦门大学 | 抗hpv l2 蛋白的广谱中和单克隆抗体或其抗原结合片段及它们的用途 |
| CN105367652A (zh) * | 2015-07-23 | 2016-03-02 | 北京生物制品研究所有限责任公司 | 一种抗hpv16l1蛋白的单克隆抗体、其制备方法和应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Smith et al. | Antibodies from women immunized with Gardasil® cross-neutralize HPV 45 pseudovirions | |
| Stittelaar et al. | Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies | |
| Day et al. | A human papillomavirus (HPV) in vitro neutralization assay that recapitulates the in vitro process of infection provides a sensitive measure of HPV L2 infection-inhibiting antibodies | |
| CN110759973B (zh) | 一种表达非洲猪瘟病毒CD2v蛋白的细胞株及其应用 | |
| CN105713087B (zh) | 人乳头瘤病毒58型单克隆抗体及其应用 | |
| van Poelgeest et al. | Distinct regulation and impact of type 1 T‐cell immunity against HPV16 L1, E2 and E6 antigens during HPV16‐induced cervical infection and neoplasia | |
| WO2019047608A1 (zh) | 一种鸭坦布苏病毒e蛋白截短蛋白及应用 | |
| CN115746130B (zh) | 鸭呼肠孤病毒单克隆抗体NDRV-σC及其检测试剂盒和应用 | |
| JPH04503153A (ja) | 新しい感染性嚢疾患ウィルス | |
| Harari et al. | Cross-protection of the bivalent human papillomavirus (HPV) vaccine against variants of genetically related high-risk HPV infections | |
| CN112877348B (zh) | 一种非洲猪瘟病毒CD2v胞外域重组蛋白及其应用 | |
| Smith et al. | Evolution of type-specific immunoassays to evaluate the functional immune response to GARDASIL®, a vaccine for Human Papillomavirus types 16, 18, 6, and 11 | |
| Liu et al. | Development and evaluation of a VP1-ELISA for detection of antibodies to duck hepatitis type 1 virus | |
| CN105296441A (zh) | 一种牛病毒性腹泻病毒毒株及其应用 | |
| CN101280316A (zh) | 人宫颈癌的一种治疗性疫苗 | |
| CN104531741B (zh) | 增强hpv抗原表位肽免疫原性的方法及类病毒颗粒、颗粒制备方法与应用 | |
| CN103333865B (zh) | Hpv假病毒和其试剂盒以及检测hpv中和抗体的方法 | |
| CN116102643B (zh) | 针对猴痘病毒a35蛋白的单克隆抗体及其应用 | |
| Wu et al. | Detection of HPV types and neutralizing antibodies in Gansu province, China | |
| CN102445548A (zh) | 基于五邻体蛋白的favi抗体间接elisa检测试剂盒 | |
| CN104120109A (zh) | 牛传染性鼻气管炎病毒gB抗体检测阻断ELISA试剂盒及用途 | |
| CN110646612A (zh) | 一种用于检测血清hpv抗体的试剂及试剂盒 | |
| Einstein | Acquired immune response to oncogenic human papillomavirus associated with prophylactic cervical cancer vaccines | |
| WO2022070210A1 (en) | Stable formulations of low abundance enteroviruses vaccines and process of manufacture thereof | |
| CN104198446A (zh) | 基于拯救重组狂犬病弱毒的新型中和抗体检测方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20200603 Address after: Room 359, block a, phase I, Zhongdan Ecological Life Science Industrial Park, No. 3-1, xinjinhu Road, Jiangbei new district, Nanjing City, Jiangsu Province Applicant after: Nanjing Weixi Biomedical Technology Co.,Ltd. Address before: Room 513, B2 Floor, 218 Xinghu Street, Suzhou Industrial Park, Jiangsu Province Applicant before: Y-CLONE MEDICAL SCIENCE Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20220425 Address after: 215101 room 513, building B2, bio nano Park, 218 Xinghu street, Suzhou Industrial Park, Suzhou area, China (Jiangsu) pilot Free Trade Zone, Suzhou, Jiangsu Applicant after: Y-CLONE MEDICAL SCIENCE Co.,Ltd. Address before: Room 359, building a, phase I, Zhongdan Ecological Life Science Industrial Park, No. 3-1, xinjinhu Road, Jiangbei new area, Nanjing, Jiangsu 210000 Applicant before: Nanjing Weixi Biomedical Technology Co.,Ltd. |
|
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200103 |