TW200918552A - Composition and method for immunization - Google Patents

Abstract

A composition for oral dosage for passive immunization of a subject against EV71 comprising polyclonal antibodies and a method for raising polyclonal antibodies against EV71 antigen in hyperimmune ungulate colostrum or hyperimmune avian eggs.

Description

200918552 IX. INSTRUCTIONS: [Technical field to which the invention pertains] This patent relates to a method for treating or inhibiting enterovirus 71 infection and a method for inhibiting transmission of enterovirus 71 infection in a group. The invention further relates to a composition for inhibiting enterovirus 71 infection and a method of preparing the composition. [Prior Art]

Enterovirus 7 1 belongs to the picornavirus family (as (10) (10) coffee (4) enterovirus (a human enterovirus A species of the genus genus. It is important to note that coffee is not a vector of animal infections. The disease includes the pathogenic factors of aseptic meningitis, encephalitis and pediatric anesthesia. The virus is also associated with large-scale human hand, foot and mouth disease. Asian countries often have _ related diseases, such as: Taiwan, Malaysia Singapore, Japan, South Korea, Thailand, Vietnam, Hong Kong, and even Australia. In 1975, the largest EV71 broke out in Bulgaria, resulting in 44 deaths; in 1978, Hungary, 45 people died; in 1997, Malaysia, Sichuan people died '1998, 2 years and 1 year ± ^ thousand and 2001, Taiwan, the death toll was 78, 25 and 26 respectively. In the plague (10 stalks, 4 ' 1998 the disease broke more than 13 Hey, a report case J includes more than 400 serious neurological cases and 78 deaths, of which 9 ** 0 f 91 疋 less than five years old. More recent explosions in early 2005 Hong Kong ^ Fun South Taiwan 'death in which a total of 31 people; early 2006 in Malaya' led to eight deaths due to its high.

Mortality and the victim are usually I horses. Volkswagen has raised concerns about EV71. 131999.doc 200918552 乂 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 用于 隔离 隔离 隔离 隔离 隔离 隔离 隔离 隔离 隔离 隔离 隔离

(Reference: Taiwan Infectious Diseases Center' Public Relations Booklet, 1999) US Patent Publication No. 2〇〇6/0292693 provides a monoclonal antibody for neutralizing EV7丨, which is administered to patients by parenteral administration. Inoculation _ seedling (passive vaccination). In order to reduce the immune response of the patient's bloodstream, individual antibodies are humanized. Therefore, the vaccine formulation phase #昂# and the requirements of the parenteral administration method make it difficult (4) to provide economically beneficial ethnic control. Moreover, although the ~71 infection originated in the intestine, the US 〇〇 咖 叙述 叙述 叙述 叙述 叙述 EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV EV However, it is best to develop the immunity of the population to pathogens when preventing clinical cases. In order to avoid the widespread prevalence of S diseases, it is important to reduce their transmission rate among people. It is highly desirable to use a) to reduce the infection rate of healthy people and b) to reduce the bioactive agent that is contaminated by the infected person. Further, due to the lack of acceptable safety information, vaccines are generally not recommended for children under 13 months of age. Similarly, for most vaccines, the immune correlation and adequate protection are gradually developed only after multiple doses. 131999.doc 200918552 The discussion of documents, stipulations, materials, devices, articles, etc., which are included in this specification, is only a context of the invention. It does not suggest or represent any or all of the substances that form part of the prior art or a part of the general related art, and is related to the present invention, as in the prior state of each application of the present application. . SUMMARY OF THE INVENTION In one embodiment, we provide a composition for oral immunization of an individual against oral administration of EV71 comprising the production of antibodies against EVS 71 antigen from colostrum or avian eggs of ungulates. In one embodiment, we provide a method for passively immunizing an individual against EV71, comprising: providing a hyperimmune substance comprising a plurality of antibodies produced by inoculating bovine or bird with EV71, and orally administering the individual to the individual The spicy antibody. The EV7m seedlings used to inoculate animals are typically selected from the group consisting of inactivated vaccines or antigenic capsid proteins of EV7i, such as the group of capsid proteins νρι. In another embodiment, we provide a method of preparing a passive oral vaccine to immunize an individual against EV71 infection, the method comprising: immunizing an animal selected from the group consisting of bovine and avian with a continental antigen; and collecting selected from bovine colostrum and poultry The hyperimmune substance of the egg, the hyperimmune substance ^ ^ s against the multi-strain antibody of the EV71 antigen. It is preferable to use a plurality of antibodies for oral administration, such as food or food additives, capsules, and the like. In another embodiment, the use of an oral preparation for forming a plurality of antibodies against an antibody against a plurality of antibodies is used for the preparation of an individual for passive immunization against an oral vaccine against EV71 infection of 131999.doc 200918552; The oral preparation for oral administration preferably comprises bovine colostrum. In another embodiment, there is provided the use of EV71 for the preparation of a passive vaccine comprising a plurality of antibodies 'for oral administration' to immunize an individual against EV71 infection, wherein the plurality of antibodies are produced by selecting a bovine animal and a poultry Animal animals inoculated with EV71 antigen 'collecting substances selected from bovine colostrum and avian eggs, which are hyperimmune on a plurality of antibodies against the EV71 antigen. The individual vaccinated with the passive vaccine is preferably a human individual. In one embodiment of the invention, the passive vaccine is administered concurrently with an active vaccine (active vaccinati). In general, the active vaccine of the EV7 丨 antigen requires a period of time to confer immunity through the production of antibodies to the active vaccine in vivo. The passive vaccine described above can be used as a measure to suppress the prevalence of infection*EV7l infection at a critical stage after becoming apparently infected. In one embodiment, the oral formulation is administered periodically for at least 20 days during the high-risk period. The high-risk period of the towel may include a period of substantial occurrence of pathogens, or until the period prior to completion of the active vaccine process. It is best to administer the oral lotion for 40 days. In a preferred embodiment, the oral formulation is at least one day old and/or human. In a preferred embodiment, the oral formulation is administered immediately before, during or after the staple food. [Embodiment] The composition includes an EV71 antigen. The EV71 antigen may comprise, for example, a group selected from the group consisting of an inactivated intact virus and one or more EV71 diseases 131999.doc 200918552 toxic capsid protein (e.g., capsid protein νρι). The term "hoofed" refers to the four-legged, subfamily, hoofed and vegetative mammal. The organism raises a range of medium to large ungulates. Bovine, yak, and four-horned and helio-horned antelopes (one, this includes colostrum milk (one ^ 及 ^ and ( four) ^ cell debris, lactose and road protein colostrum milk; ^ method = · cold; east Drying, spray drying or other colostrum milk or processed colostrum well known in the art. Colostrum milk is usually taken from cows with hoofs such as five cents after splitting. In one embodiment, people:, The composition of the patient comprises a colostrum in a dry form. The composition may be selected from the group consisting of adjuvants, carriers, drugs and other active ingredients, and is mixed before, during or after the drying process. The composition of the package: can be dried by cold, Eastern drying or other methods known in the art for drying colostrum. The composition for administration to an individual can be a hyperimmune substance, but preferably derived from a hyperimmune substance. For example, in the case of colostrum, the composition administered to the individual may be treated by a specific operation, more preferably by using a degreasing operation and removing, 'field breaking shoulders' operation, more preferably for use. Lipid prevention operation, removal of cell debris and removal of salt Operation of sugar, other low molecular weight substances and some water. In the entire text of this manual and in the application, 'words" includes "(l,compdse)) and /, variations (including ("compnsing", "comprises") It is not intended to exclude other additives, ingredients, entities or steps from I31999.doc 200918552. The present invention relates to the provision of a plurality of sputum containing EV71 antigens, and the composition is preferably derived from hoofs. An animal-like substance and a hyperimmune substance in the group of egg yolks of poultry eggs. The oral preparation comprises a plurality of antibodies or a binding fragment thereof, wherein the plurality of steroids are derived from colostrum of ungulates or egg yolk. Preferably, the oral preparation is taken from at least partially purified bovine colostrum that has been inoculated against at least one vaccine or vaccine from the EV71 antigen. The vaccine for producing a plurality of antibodies can be administered to bovine animals and can comprise At least one inactivated EV71 virus and £:¥capsid protein, such as capsid protein VP1. The composition may comprise one or more adjuvants. The adjuvant may be containing eighteen carbons An immunostimulant composition of an acid and an ester of dehydrated mannitol. Examples of other adjuvants include aluminum hydroxide or incomplete Freund's adjuvant or ISCOMS. The vaccine preferably includes the M〇ntanide adjuvant or a similar multiphase adjuvant. For example, the adjuvant may be "M〇ntanide ISA 2〇6 vG", an APVMA-approved and veterinary adjuvant supplied by Seppic, supplied by Tan Bennett, Australia. Montanide ISA 206 VG is contained in an oily solution. An immunostimulant composition of an ester of octadecenoic acid and dehydrated mannitol. When the multi-drug antibody is derived from hyperimmune colostrum, the colostrum is collected within 3 weeks after delivery, and is more suitable within 1 day after delivery. Suitable, the first lactating colostrum is most suitable. For example, 'each oral preparation may contain less than 8 mg (dry weight) of the initial milk equivalent' less than 400 mg, preferably less than 200 mg. Colostrum equivalent means the amount of unprocessed colostrum, however after treatment at 131999.doc 200918552 'processed to provide the content as a formulation. In the example, the amount of the multi-strain antibody in the composition is sufficient / and the composition is at least 1 > 5 wt% specific for the antigen. The immunoglobulins are, for example, at least 2% by weight or at least 3% by weight of the composition, up to 25 parts by weight. Or up to 2% by weight. 6 Hai oral preparation preferably includes from hyperimmune colostrum and / or according to

The contents of the 14 patents are incorporated by reference into pCT/AUG3/()() 348 (publication number: Wq/2q café teaches the addition of colostrum to the multi-drug antibody. The oral preparation may also contain : disclosed in 2005/001746 (publication number: w〇/2QQ6/()53383), the oral preparation is used in combination with an active vaccine scheme involving the use of an active vaccine against pathogens. For the vaccination active vaccine protocol and the period prior to completion of the reaction. In a preferred embodiment, the oral composition comprises a multi-strain antibody against at least one surface antigen of the virus taken from the Group #71 group. In the most risky period, for example, in summer, the oral preparation is suitable for regular administration at least for a period of at least 4 days, and more preferably at least 0 days. The multi-strain system is used by using an EV71-containing antigen (eg, extinction). Vaccination of live intact EV71 and/or EV71 capsid proteins, such as: νρι-like protein, from ungulates and avian animals. The antigen may comprise one or more selected from inactivated intact EV71 Type 8, from EV7i 3 A group consisting of a protein (eg, VPI), an inactivated intact EV71 c-type, and a protein from ev7! C3L (eg, vp丨). The polyclonal antibody is preferably 131999.doc 12 200918552 for each At least one antigen of enterovirus 71 type B antigen and an enterovirus 71 c-type antigen are produced. The vaccine preferably comprises an inactivated intact EV71 virus. In another preferred embodiment, the vaccine comprises inactivated The virus and the surface antigen VP1 are further included. The antibody preferably comprises antibodies produced against EV71 type B antigen and type C antigen, respectively. The composition may be selected from food or food additives, tablets, syrups, capsules and film coats. The composition of the group of the ingots. The composition of any of the items of the present invention is in the form of a particle mixed with a food or a beverage. The composition of any one of the preceding claims, wherein the multi-drug antibody It is present in a carrier derived from colostrum. The colostrum used to provide multiple antibodies is preferably collected from individual animals in separate containers. 'Before collecting, the colostrum from each container is tested separately. From the beginning of each animal Milk best The cold beads are separated. The method and apparatus for collecting colostrum have been described in Pub. No.: WO/20〇4/1〇785U International Application No.: pCT/AU2〇〇4/〇〇〇773), the disclosure of which has been The citations are incorporated herein by reference. In one embodiment, the pooled dry colostrum has a neutralization titer of at least 1:2 Torr for at least one of B and EV71C, suitably 1:4 Torr, more suitably 1:100, 1:200, and more suitable. The neutralization test involved "TCIDSO" neutralization analysis (1 (: 1〇5〇 = 5〇% tissue culture infectious dose). In this analysis, the dilution of the anti-EV71 colostrum powder in 1%% solution Mixed with 100 TCID50 £¥71 virus. For the report and 131999.doc •13- 200918552 valency' to form an undiluted reference solution with this ίο% solution (ie ι: 2 〇 neutralization titer means 10%) The solution needs to be diluted 1:2 〇 (or lower) to achieve neutralization. After a period of incubation, these colostrum and virus mixtures are added to a plate containing kidney cells that serve as host cell-transfer virus growth. When the active virus is in contact with the host cell, it is easily changed by the cytopathic effect (CPE) by attaching it to the cell surface Φ and causing the cell to eventually cause cell death. CPE is in the cell (due to Viral infection) Any detectable change, including rounding, swelling, shrinking, dying, or detachment of the cells. The oral formulation of the antibody is preferably a finely divided powder that can be mixed with food or beverage. In another preferred embodiment , the antibody mouth The formulation is present in the inclusion body which can be added to the food, preferably a non-heated food. The size of the inclusion body which can be added to the food is greater than 10 microns, more preferably greater than 100 microns, and more preferably greater than ! mm. Preferably, the inclusion body is in a non-heated food such as a cream or jelly or a milk beverage made from a powder. The inclusion body comprising the antibody preferably further comprises another palatable ingredient such as chocolate. Confectionery or other food ingredient. The present invention is particularly advantageous for controlling outbreaks of EV71 infection in disease populations, particularly those involving children. Thus, in one embodiment, the method comprises inhibiting outbreaks of EV71 in a disease population, including direct Children and their families exposed to infected individuals are orally administered with multiple antibodies. The composition preferably administers at least 30% or at least 50% of the population in the population. 131999.doc -14-200918552 is better in the disease population All of the members of the present invention are described by the following examples. It is to be understood that the following examples are provided to illustrate the invention, but in no way limit the scope of the invention Example 1 An antibody formulation was prepared which was active against EV71 c (Taiwan strain). The EV71 virus was placed in a cell culture flask in the presence of Vero, ', Endogenous & ' in a mem growth medium to prepare a bovine vaccine. The growth medium is hydrolyzed with a trypsin solution by removing the particulate matter from the u step. The liquid is superfluidized in the cross-flow system to remove fragments less than 9 KDa. The formalin treatment step and the bei treatment step inactivate the remaining large components. Prepare the bovine vaccine according to the following sequence: 1) Expand the Vero cells (prefabricated method) Make a serum-free medium (Viral Productic) I1 Senjm Ffee Media) Culture of a series of yer〇 cells on Cytodex 1 microcarrier beads 2) Start production of Vero cell cultures - using Cytodex 1 microcarriers and vp_SFM. 3) Infecting fusion cells with EV71 - Infection test virus strain M〇 l=〇. 〇〇1. 4) Collect medium SN, rinse beads and filter purification - After 48 hours of infection, allow the beads to settle and collect the medium SN through a stainless steel sieve (1) um um), a deep filter (~5 um) and a 0.8/0.2 um filter. The beads were washed with 2X 1/4 volume PBS, filtered through medium SN and pooled. 5) Test virus titer, contaminant (mycoplasma/bacteria/fungus) and sterility 6) Enzymatic hydrolysis with trypsin 131999.doc -15- 200918552 7) Inactivation with hydrazine and formaldehyde 8) Using a 100 KDa filter Tangential flow filtration 9) Collection of purified and concentrated TFF retentate of EV71 antigen 1 〇) Purity, sterility and inactivation were tested for purity - SDS-PAGE gel, Western blot analysis; antigen potency - ELISA inactivation - Inoculation of Vero cells to detect virus inactivation 11) Filtration by 0.2 um filter - test bacteria, fungal sterility and mycoplasma contamination 12) Combination use yjontanide 206 adjuvant with EV71 antigen _ Final sterility check / no fuma Lin test/safety test/vaccine release A mixture of the obtained antigen and Montanide adjuvant is injected into the body during the last trimester of the bovine pregnancy at least twice every 2 weeks. The colostrum produced after the delivery of the cattle is collected using the system described in U.S. Publication No. 2〇〇6〇249〇84. The liquid colostrum is further processed in a system described in U.S. Patent Publication No. 2, No. 5,391,917 to produce a freeze containing at least 3 % IgG.

Heterologous immunoglobulin. Example 2 Neutralization titer of multiple antibodies prepared according to the method of Example 1.

131999.doc -16· 200918552 A mixture of colostrum and virus into a culture plate containing kidney cells that act as host cells to maintain viral growth. When the active virus is in contact with the host cell, it is susceptible to infection by attaching to the cell surface and causing a change in cytopathic effect (CPE) i which ultimately leads to cell death. cpE is any detectable change in cells (due to viral infection), including rounding, swelling, shrinking, dying, or detachment from the surface. It has been found that when colostrum containing a specific antibody is added to the virus, EV7 1 is neutralized and its ability to infect cells is reduced. For the colostrum powder of Example 1, a dilution of 1:25 was found to neutralize EV71 and inhibit typical CPE of at least 50% of the virus. This neutralization analysis (see table below) requires only 1 〇 mg of the colostrum powder of Example 1 to neutralize 106 pfu of EV71C. EV71C Taiwan strain was determined by EV71 antibody from Example 1.

Enter virus* (10V0.1 mL) Use EV71 to immunize colostrum and obtain TCID5〇/〇.l mL control group (not neutralized) 10 mg/0.1 mL 1 mg/〇.l mL 7.5 6.8, 6.68 (Average Value 6.74) 7.55, 7.16, 7.55 6.5 <2.8, 0.8, 1.41 (average 1.20) 5.68 5.5 <1.8, N 4.15, 4.01 (average 4.08) 4.5 N 2.3, 1.16 (average 2.03) 3.5 NN 2.5 NN "N" means not detected 131999.doc 17 200918552 Example 3 Antibody potency in animal models: It is ethically unacceptable for children to be children because they require children to be exposed to harmful viruses in geographically unpredictable epidemics The efficacy of the loops challenges clinical trials, and the natural disease is only the environment, so the animal model that uses the EV-71 strain to challenge mice is developed. Before using the i()6 tci~e^7ic challenge dose, give a group of years of Balb/C mice oral 2 实例 example!

Colostrum powder (200 ul 100 mg/ml suspension). 5 groups of Balb/c adult mice in each group: Treated according to the following table: 1~~ 1 Only EV71 C Taiwan (passage 8 times) (1〇6) - 2 EV71 C+ immune colostrum (Pre-neutralization) 3 EV71 C+ Immune colostrum (infection ~ Group 3 was inoculated with 2 〇 mg £¥71 to immunize colostrum by gastric tube, and after 1 hour, Group 1 and Group 3 were inoculated with 200 EV71C, respectively. Taiwan (including 1〇6 TCID50). Group 2 uses a gastric tube to infuse 2〇() μ pre- and EV71C (containing a pre-culture mixture of 1〇6 TCID5々2() mg EV71 immune colostrum). During the 6-hour period, each feces of each mouse was collected. The feces were collected separately and returned to the hour of each hour. The stool samples were resuspended in the medium and 00 uL of chloroform was added to each. In the sample, the supernatant was collected and diluted to analyze the virus retention. I31999.doc • 18- 200918552 Result: Adult mouse test group fecal fraction -- lh 2h 3h -Si - substance 1 - infection only (10 , * J5h white mouse 1 white mouse 2 - _ + - + white mouse 3 - - white mouse 4 white mouse 5 + + + + one + 2 - pre-neutralization ^ - Mouse 1 Mouse 2 - - - * • Mouse 3 . - - Mouse 4 + - - Mouse 5 . - - 3 Use colostrum 1 hour before infection 1 Mouse 2 - - - + • White mice 3 Ten white mice 4 - - White mice 5 - One - "Ten" stagnation is a disease of the existing silkworms ~ ~ --- No virus found in the feces The adult mouse study proves: 1 〇 6EV71c challenge dose only 20 mg EVProtec colostrum powder can be used for pre-neutralization, and all the mice except the mice are kept in the tenth state after passing through the gastrointestinal tract. All the mice in the third group (infected, not using colostrum) ) showed that in the third group of mice whose faeces contained important 'first (with gastric tube feeding) vaccination, before receiving EV71C challenge H, when receiving 2 〇mgEvpr〇tec colostrum powder, 'white gastrointestinal tract EV7丨c, which also neutralizes the challenge. Finally, it should be understood that various other modifications and/or changes can be made without departing from the spirit of the invention. 131999.doc • 19-

Claims (1)

200918552 X. Patent application scope: 1. An oral preparation composition for passively immunizing an individual against EV71, which comprises a plurality of antibodies against EV71 antigen derived from colostrum of a hyperimmune ungulate animal Or hyperimmune poultry eggs. 2. A composition according to any of the preceding claims, which is in the form of a group selected from the group consisting of foods, food additives, tablets, syrups, capsules and film ingots. The composition of any of the preceding claims, which is in the form of granules which may be mixed with food or beverage. 4. The composition of any one of the claims, wherein the plurality of antibodies are present in a vector derived from colostrum. 5. The composition according to any one of the preceding claims, wherein the composition further comprises at least one selected from the group consisting of Montanide adjuvant, aluminum hydroxide, incomplete Freund's adjuvant and 1SCOMS. Agent. 6. A composition according to any of the preceding claims, wherein the individual vaccinated with passive vaceination is a human. 7. The composition according to any one of the preceding claims, wherein the plurality of antibodies are derived from the hyperimmune colostrum collected within days after the delivery of the knife, and are more suitable for the first day after delivery, with the first milk of the first lactation Most suitable. 8_ </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; An immunoglobulin specific for an EM antigen. 9. The composition of any of the preceding claims, wherein the multi-strain antibody is present in the dried colostrum, P, Lu,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Doc 200918552 Undiluted Reference) The neutralization titer for at least one of EV71B and EV7 1C is at least 1:20' suitably 1:40, more suitably 1:1, and 1:200 is more preferred. 10. The composition of any one of the preceding claims, wherein the oral preparation comprises a unit dose containing less than 800 mg (by dry weight) of colostrum equivalent, less than 400 mg being suitable ' Less than 2 〇〇 mg is more suitable. The composition of any one of the claims, wherein the EV71 antigen comprises a complete EV71 C type selected from the inactivated intact EV71 B type, the EV71 B type capsid protein (eg VP1), inactivated, and One or more of the group consisting of EV71 Type C (eg, VP1). The composition according to any one of the preceding claims, wherein the plurality of anti-systems are produced for at least one antigen of each enterovirus 71 type antigen and an enteric virus type 7丨C type antigen. 13. The composition of any of the preceding claims, wherein the oral preparation is administered at a high risk for a period of at least 2 days, wherein the high risk period comprises a period of large number of pathogens occurring or a period prior to completion of the active vaccine process Preferably, the oral preparation is administered on a regular basis for 4 days. 14. A method of treating or inhibiting an individual infected with EV7i, # comprising orally administering to the individual a composition according to any one of the preceding claims. κ 15. A method for preparing a passive oral vaccine to immunize an individual against EV71 infection, comprising: immunizing with a EV71 antigen from a bovine animal and an avian animal; and collecting hyperimmune from the animal selected from the group consisting of bovine colostrum and a scorpion egg In no case, the hyperimmune substance contains a plurality of antibodies against the EV71 antigen. &quot; 131999.doc 200918552 1 6. The method of claim 5, wherein the multi-drug antibody is derived from the hyperimmune colostrum collected within 3 days after delivery, and is more suitable within 1 day after delivery, at the beginning of the first lactation Milk is most suitable. 1 7. The method of claim 5 or 丨6 wherein the EV7丨 antigen comprises an inactivated virus and further comprises a surface antigen νρι. 18. The method of any one of clauses 15 to 17, wherein the EV71 antigen comprises a complete EV71 C type selected from the group consisting of inactivated intact EV71 B type, EV71 type B capsid protein (eg, VP1), inactivated And one or more of the group consisting of EV71 type C vaginal proteins (eg, VP1). 19. The method of any one of claims 15 to 18, wherein the plurality of anti-systems are produced against at least one antigen of each enterovirus 71 type B antigen and an enteric virus type 71 C antigen. The method of any one of claims 15 to 19, wherein the oral preparation comprises a unit dose containing less than 800 mg (by dry weight) of colostrum equivalent, less than 400 mg being suitable, less than 2 〇〇. Mg is more suitable. The method of any one of claims 15 to 20, wherein the oral preparation is used in combination with an active vaccination regimen involving the use of an active vaccine against a pathogen. 22. The method of claim 21, wherein the oral preparation is for use The vaccination active vaccine program and the period before the completion of the reaction. 23. The method of any one of clauses 15 to 22, wherein the plurality of antibodies form an oral preparation form ... food or food additive, tablet, syrup, capsule or the like. 24. The method of any one of clauses 15 to 23, wherein the animal is vaccinated with inactivated ev7i 131999.doc 200918552. The method of any one of claims 15 to 24, wherein the dry colostrum has a neutralization titer of at least one of EV71B and EV7 1 C of at least 1: (20% by weight of the colostrum dry matter), suitably 1:40, more suitably 1:1 〇〇, 1:2 〇〇 is more suitable. The method of any one of claims 15 to 25 which is directed to inhibiting the outbreak of EV71 in the EV71 disease population comprising oral administration of multiple antibodies to children and their families directly exposed to the infected individual. 27. Use of (1) a composition according to any one of claims 1 to 14 and (8) an active vaccine for the preparation of a medicament or agents for treating or preventing EV71 infection. 28. The use of claim 27, wherein the use is to inhibit the outbreak of EV71 infection in the EM disease population by oral administration of multiple antibodies to children and families directly infected with the individual. 29. The use of claim 27 or 28, wherein the composition is administered to an individual of at least 30% (preferably at least 50%) of the group. 30. The use of any one of claims 27 to 29, wherein A Dan T administers the composition to all members of the disease group. - a kit for immunization against infection, #includes (1) an oral preparation of a composition according to any one of claims (1) and (8) comprising at least one selected from the group consisting of an intact antigen, an inactivated antigen, and a dansone or a plurality The part of the active vaccine. 32. The kit of claim 31, which is accompanied by instructions for using the oral preparation prior to use. Prior to the use of the active vaccine, 131999.doc 200918552 33. A method for passive oral vaccination against an individual to combat £¥71 infection, comprising: collecting from an animal selected from the group consisting of cattle and avian animals immunized with the EV71 antigen a hyperimmune substance of colostrum and avian eggs, the hyperimmune substance comprising a plurality of antibodies against EV71; and the oral administration of the plurality of antibodies to the individual. 34. The method of claim 33, wherein the composition is in a form selected from the group consisting of foods, food additives, tablets, syrups, capsules, and film ingots. The method of claim 3, wherein the composition is in the form of particles which can be mixed with food or beverage. The method of any one of items 33 to 35, wherein the plurality of anti-systems are mixed with the substance derived from colostrum. The method of any one of clauses 33 to 36, wherein the composition further comprises at least one group selected from the group consisting of Montanide adjuvant, aluminum hydroxide, incomplete Freund's adjuvant, and ISCOMS. Group of adjuvants. 38. The method of any of clauses 33 to 36, wherein the individual vaccinated with the passive vaccine is a human. For example, the method of any one of the items 33 to 37, wherein the plurality of antibodies are derived from the hyperimmune colostrum collected within 3 days after the splitting, is more suitable on the 1st day after delivery, and is most suitable for the first lactation. . ^7 The method of any one of the items 33 to 38 wherein the plurality of antibodies are present in the dried colostrum. The dry colostrum is at least 1:2 〇 for at least one EV71 B and EV7 1C. The ground is 1:4 〇, more suitably 1:1 〇〇, 131999.doc 200918552 1:200 is more suitable. 41. The method of any of clauses 33 to 4, wherein the unit dosage comprising oral administration comprises less than 800 milligrams (by dry weight) of colostrum equivalent, less than 400 milligrams is suitably 'less than 2 milligrams More suitable. 42. The method of any of clauses 33 to 41, wherein the oral preparation is administered periodically for a period of at least 20 days during a high-risk period, the period of high risk comprising a period of occurrence of a plurality of pathogens or a period prior to completion of the active vaccine process , ^ Good time to the oral preparation for a period of 40 days. 43. Use of any of the items 33 to 42 and active vaccine against pathogens. The method of the present invention, in combination with the vaccination active vaccine regimen used. 44. The method of claim 42, wherein the oral formulation is administered by a vaccine regimen and a period prior to completion of the reaction. The method of any one of claims 33 to 44, wherein the composition is administered to members of the £, 71 disease group. l. 46. Use of a plurality of antibodies against EV71 for the preparation of an oral vaccine for immunizing an individual against EV7i infection by forming an oral preparation form of a plurality of antibodies, preferably in the form of an oral preparation for the individual 2 Colostrum 47. The use of EV7 in the preparation of a passive vaccine comprising an oral multi-drug antibody for immunizing an individual against EV71 infection, wherein the multi-incacter antibody system is inoculated with eV71 from a bovine animal And avian kinetics = and collects substances selected from bovine colostrum and avian eggs, which are hyperimmune on antibodies against EV7 1 . 131999.doc 200918552 48. For the use of claim 46 or 47, the individual vaccinated with the passive vaccine is of the class. 49. For the use of claim 47 or 48, the administration of the passive vaccine is carried out simultaneously with the vaccination of the primary vaccine. 50_ A method of inhibiting the outbreak of EV71 in an EV71 disease group, comprising orally administering a plurality of antibodies to a child and a family member who are in contact with the infected individual. Human movement straight 131999.doc 200918552 VII. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best display. Chemical formula of the invention: (none) 131999.doc