CN101559223A - Idemic encephalitis diphtheria-pertussis-tetanus combined vaccine - Google Patents

Idemic encephalitis diphtheria-pertussis-tetanus combined vaccine Download PDF

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CN101559223A
CN101559223A CNA2008100875987A CN200810087598A CN101559223A CN 101559223 A CN101559223 A CN 101559223A CN A2008100875987 A CNA2008100875987 A CN A2008100875987A CN 200810087598 A CN200810087598 A CN 200810087598A CN 101559223 A CN101559223 A CN 101559223A
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group
vaccine
epidemic encephalitis
combined vaccine
combined
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CN101559223B (en
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蒋仁生
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ANHUI ZHIFEI LONGCOM BIOPHARMACEUTICAL CO., LTD.
Chongqing Zhiren Biotech Company Ltd.
Beijing Zhifei Lvzhu Biopharmaceutical Co Ltd
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CHONGQING ZHIREN BIOTECH Co Ltd
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    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to an idemic encephalitis diphtheria-pertussis-tetanus combined vaccine, in particular to a combined vaccine which takes B group meningococcus outer membrane protein as a core, contains other group meningococcus coupling or uncoupling amylase antigens, and is formed by an idemic encephalitis vaccine and a diphtheria-pertussis-tetanus vaccine. The combined vaccine further contains hepatitis B virus antigens and inactivation poliovirus antigens. The combined vaccine is suitable for preventing infection caused by epidemic meningococcus and diphtheria-pertussis-tetanus interrelated pathogenicbacteria in crowds, can further prevent the infection caused by hepatitis B viruses and polioviruses, reduces the immunity injection times through multiple polyvalent vaccine immunization and lowers the secondary reaction frequency of vaccine inoculation.

Description

Idemic encephalitis diphtheria-pertussis-tetanus combined vaccine
Technical field
The technology of the present invention field can relate to epidemiology, Medical Microbiology, immunology, vaccinology, preventive medicine, prevents a kind of or the microbial disease of several cause of diseases by immunity inoculation.
The present invention relates to a kind of brand-new combined vaccine, the associatings of a kind of vaccine of epidemic menigitis and white hundred broken vaccines can prevent epidemic cerebrospinal meningitis coccus, diphtheria, the pertussis of A, B, C, W135, Y serotype, the infection of clostridium tetani simultaneously.Combined vaccine of the present invention also further comprises antigen of hepatitis B virus and inactivated poliovirus antigen, can further prevent the infection of hepatitis B virus and poliovirus.Combined vaccine can reduce immune pin, reduces immune cost, increase the acceptability of vaccine, thereby enlarges immune coverage rate.
Background technology
Meningococcus mainly causes the generation of human body epidemic cerebrospinal meningitis, also can cause other respiratory tract diseases such as pneumonia.Pathogenic bacteria is present in patient or bacillicarrier's the nasopharyngeal secretions, infects by respiratory tract.Epidemic encephalitis popular has obvious seasonal and periodically, and winter-spring season sickness rate height generally begins morbidity from annual January, and be the peak period March or April.According to statistics, annual 2 to April, and it is annual about 60% that the sickness rate of " epidemic encephalitis " accounts for, and be characterized in that onset is anxious, the state of an illness is heavy, it is many to change, propagate and fast, popularly extensively break with tremendous force, the case fatality rate height, hazardness is big.The crowd all can be taken place in each age group crowd the general susceptible of epidemic encephalitis coccus, but better sending out in little age bracket child, the patient mainly is the children below 15 years old, particularly 6 months to 2 years old infant.In recent years, also finding clinically has the adult to suffer from this disease, and adult's case fatality rate height.
Epidemic encephalitis has 13 sero-group types, and wherein A, B, C and W135 type can cause eruption and prevalence.In Africa and area, Asia, for many years, epidemic encephalitis is all preponderated with the A type, and especially from Senegal, on area, Ethiopic African the Sahara " epidemic encephalitis band ", the Mongolia in Asia also reported once in 1994-1995 is very popular.The popular of other serotypes also happens occasionally, 2000-2001 but recently,, hundreds of names have infected the epidemic encephalitis that W135 causes,, the Burkina Faso in Africa in 2002 to Saudi haj person, 13000 patient infections W135 serotype epidemic encephalitis, cause 1500 death.Only 2002 1 year, the epidemic encephalitis case of World Health Organization's report reached 223000 examples.Epidemic encephalitis not only betides Asia and Africa, and also very common in North America and Europe, especially B group accounts for the over half of epidemic encephalitis case.Y group also can cause meningitis in child and teenager, but compares with other types, and it is easier to cause pneumonia in big age cohort, and in recent years, the disease that Y group's serotype causes comes back year by year in the U.S..
China also belongs to the hotspot of epidemic encephalitis, and nearly more than 30 years data shows that A group bacterium is the popular dominant bacteria of China always, sickness rate non-popular year be 3-10/10 ten thousand, capable year of rill is 30-50/10 ten thousand, the year of being very popular is up to 100-500/10 more than ten thousand.Since the nineties in last century, B group's epidemic encephalitis proportion is enlarging gradually, and especially in developed regions, epidemic cerebrospinal meningitis is more and more obvious to B group's bacterial type transition by A group.2000, C group's epidemic encephalitis also presented expansion trend at home, and 2004-2005, it is popular that China has 7 groupment epidemic encephalitiss, and wherein 5 are caused by C group, and 1 is A group, and 1 not quite clear.
Vaccine at epidemic encephalitis mainly contains epidemic encephalitis polysaccharide vaccine, epidemic encephalitis GL-PP combined vaccine and epidemic encephalitis 1 outer-membrane protein vaccine, at serotype comprise A, B, C, W135 and Y.Polysaccharide vaccine is not owing to a little less than the immunogenicity, be adapted at the routine immunization of this age cohort in child below 2 years old.The proteinpolysaccharide combined vaccine is converted into the T cell dependent type with the immunne response that polysaccharide antigen stimulates from T cell independent form, can use in the littler age cohort, the existing in the world epidemic encephalitis combined vaccine at A, C, W135 and Y.B group's polysaccharide do not produce immunne response substantially in human body, but a kind of improved B group's GL-PP combined vaccine is developed also because a composition in structure and the human nerve tissue is similar.The outer membrane protein of epidemic encephalitis also is a kind of protective antigen, and a plurality of national registrations use B group's epidemic encephalitis 1 outer-membrane protein vaccine in South America, has also fully proved the safety and the protection effect of vaccine in the use of Norway.External also have a plurality of mechanisms carrying out the 1 outer-membrane protein vaccine development of A group and other sero-group types.At present, the vaccine of epidemic menigitis of China's approved listing comprises A group's epidemic encephalitis polysaccharide vaccine, A+C epidemic encephalitis polysaccharide vaccine, ACW135Y epidemic encephalitis 4 valency polysaccharide vaccines, AC epidemic encephalitis combined vaccine, and A group's epidemic encephalitis combined vaccine, ACW135Y tetravalence epidemic encephalitis combined vaccine, B group's epidemic encephalitis combined vaccine, A group's epidemic encephalitis 1 outer-membrane protein vaccine, B group's epidemic encephalitis 1 outer-membrane protein vaccine are in active development.
White hundred broken be at diphtheria, pertussis and tetanic prevention preparation, use has for many years both at home and abroad fully proved its safety and protection effect, is in the national The Immune Programming always, the goods that fundamental immunity comprised.White hundred broken vaccine compositions comprise diphtheria toxoid, pertussis composition, tetanus toxoid, according to the pertussis composition be the full cell of deactivation also or component divide into two kinds white hundred broken vaccines, a kind of is full cell white hundred broken vaccines, and another kind is acellular white hundred broken vaccines.In China, full cell white hundred broken vaccines and acellular white hundred broken vaccines all have launch.
Multi-joint multivalence is a direction of vaccine development.Along with science and technology development, when safer, effective, quality controllable replacement vaccine occurred like the mushrooms after rain, more and more the novel vaccine at other infectious disease also was developed.The appearance of novel vaccine has enlarged the human kind that keeps off infection, but the thing followed is the lifting significantly of immune time, need use the pin that reduces immunity by uniting of vaccine.Combined vaccine has made things convenient for immunity inoculation, has strengthened the acceptability of vaccination, has also reduced the inoculation cost, can improve the inoculation coverage rate of vaccine.
Idemic encephalitis diphtheria-pertussis-tetanus combined vaccine is a kind of brand-new combination, can prevent the infection of different shaped epidemic encephalitis diplococcus, diphtheria corynebacterium, Bordetella pertussis, clostridium tetani simultaneously.Epidemic encephalitis A, B, C, W135, Y polysaccharide or protein vaccine unit price or multivalence and white hundred broken associatings, especially polysaccharide antigen exists with the form that is coupled to carrier protein, can use widely on the crowd, can making things convenient for from now on, country brings it in The Immune Programming of expansion into.
Summary of the invention
The present invention relates to a kind of brand-new combined vaccine, a kind of is associating core and that comprise other group meningitis cocci coupling or non-coupling polysaccharide antigen and white hundred broken vaccines with B group meningitis cocci outer membrane protein, can prevent epidemic cerebrospinal meningitis coccus, diphtheria, the pertussis of A, B, C, W135, Y serotype, the infection of clostridium tetani simultaneously, satisfy above-mentioned needs.Combined vaccine of the present invention also further comprises antigen of hepatitis B virus and inactivated poliovirus antigen, can further prevent the infection of hepatitis B virus and poliovirus.
On the one hand, a kind of combined vaccine, it is characterized in that, described combined vaccine comprises vaccine of epidemic menigitis and DPT vaccine, wherein said vaccine of epidemic menigitis be with B group meningitis cocci outer membrane protein composite by core and comprise other group meningitis cocci and formed with a protein carrier coupling or non-link coupled polysaccharide antigen.Wherein, described polysaccharide antigen derives from A, C, W135, the Y group meningitis cocci a kind, 2 kinds, 3 kinds or 4 kinds of capsular polysaccharide antigen and B group meningitis cocci outer membrane protein composite; Described B group's outer membrane protein composite is 1 valency, divalent or the multivalence outer membrane protein composite that derives from B group meningitis cocci different shaped bacterial strain.Further, described capsular polysaccharide is to exist with a carrier protein couplet form or non-coupling form, and described coupling form is that polysaccharide is connected with chemical covalent bond with carrier protein, forms bonding state.This carrier protein be selected from cross reacting material in tetanus toxoid (TT), diphtheria toxoid (DT), the sudden change diphtheria toxin, diphtherotoxin (CRM9, CRM197), DT-Pa (PT), B group's epidemic encephalitis external membrane protein complex (OMP), epidemic encephalitis 64K outer membrane protein, hemophilus influenza P1, P2, P4, P5, P6 outer membrane protein, adhesin, reorganization Pseudomonas aeruginosa exotoxin A (rEPA), albumin or the blue albumen of spoon.
On the other hand, the present invention relates to a kind of combined vaccine, wherein further comprise antigen of hepatitis B virus, form epidemic encephalitis-whooping cough-hepatitis B combined vaccine.
On the one hand, the present invention relates to a kind of combined vaccine again, wherein also further comprise poliovirus antigen, form epidemic encephalitis-whooping cough-ridge ash combined vaccine.
Another aspect the present invention relates to a kind of combined vaccine, wherein also further comprises antigen of hepatitis B virus, poliovirus antigen, forms epidemic encephalitis-whooping cough-hepatitis B-ridge ash combined vaccine.
Another aspect the present invention relates to combined vaccine, wherein various compositions is sub-packed in respectively in two autonomous container, mixes inoculating when immunity; Or several compositions are prepared into independent vaccine, mix inoculating when immunity; Or just be sub-packed in the preparation in the container and become multiple vaccines.
Another aspect, combined vaccine of the present invention are any in liquid dosage form, freeze-dried formulation, capsule formulation, tablet, the pill or several.
Another aspect, combined vaccine of the present invention further comprise aluminum salt adjuvant and other adjuvants, and wherein said aluminum salt adjuvant is selected from aluminium hydroxide, aluminum sulfate or aluminum phosphate.
Again on the one hand, combined vaccine of the present invention is to carry out immunity by being selected from following mode: injection, oral, mucosa spraying or place.
In other words, emphasis of the present invention is found to be:
The first, the inventor finds, after will containing the vaccine of epidemic menigitis of A group meningitis cocci polysaccharide, C group meningitis cocci polysaccharide and B group meningitis cocci outer membrane protein composite and DPT vaccine and being mixed with combined vaccine, can strengthen the immunogenicity of pertussis antigen;
The second, the inventor finds, to contain be mixed with combined vaccine with the link coupled A group meningitis cocci of protein carrier polysaccharide, with the vaccine of epidemic menigitis of a protein carrier coupling C group meningitis cocci polysaccharide and B group meningitis cocci outer membrane protein composite and DPT vaccine after, can strengthen the immunogenicity of pertussis antigen;
Three, the inventor finds, behind increase W135 group meningitis cocci polysaccharide and the Y group meningitis cocci polysaccharide, can find that still above-mentioned first and second is described to the immunogenic enhancement effect of pertussis antigen in combined vaccine;
Four, the inventor finds, when epidemic encephalitis, whooping cough and antigen of hepatitis B virus are mixed with epidemic encephalitis-whooping cough-hepatitis B combined vaccine, except that the immunogenicity of above-mentioned enhancing pertussis antigen, also can strengthen the immunogenicity of antigen of hepatitis B virus;
Five, the inventor finds, when epidemic encephalitis, whooping cough and inactivated poliovirus are mixed with epidemic encephalitis-whooping cough-ridge ash combined vaccine, except that the immunogenicity of above-mentioned enhancing pertussis antigen, also can strengthen the immunogenicity of ridge ash virus antigen;
Six, the inventor finds, when epidemic encephalitis, whooping cough, antigen of hepatitis B virus and inactivated poliovirus are mixed with epidemic encephalitis-whooping cough-hepatitis B-ridge ash combined vaccine, except that above-mentioned enhancing pertussis antigen immunogenicity, also can strengthen the immunogenicity of antigen of hepatitis B virus and ridge ash virus antigen;
Seven, the inventor finds, epidemic encephalitis and whooping cough are mixed with epidemic encephalitis-whooping cough combined vaccine, and each immunogenicity of antigens of epidemic encephalitis is not lowered after associating;
Eight, the inventor finds, epidemic encephalitis, whooping cough and antigen of hepatitis B virus are mixed with epidemic encephalitis-whooping cough-hepatitis B combined vaccine, and each immunogenicity of antigens of epidemic encephalitis is not lowered after associating;
Nine, the inventor finds, epidemic encephalitis, whooping cough and inactivated poliovirus psma ligand are made epidemic encephalitis-whooping cough-ridge ash combined vaccine, and each immunogenicity of antigens of epidemic encephalitis is not lowered after associating;
Ten, the inventor finds, epidemic encephalitis, whooping cough, antigen of hepatitis B virus and inactivated poliovirus psma ligand are made epidemic encephalitis-whooping cough-hepatitis B-ridge ash combined vaccine, and each immunogenicity of antigens of epidemic encephalitis is not lowered after associating;
The 11, the inventor finds, epidemic encephalitis, whooping cough, antigen of hepatitis B virus and inactivated poliovirus antigen are mixed with epidemic encephalitis-whooping cough combined vaccine, epidemic encephalitis-whooping cough-hepatitis B combined vaccine, epidemic encephalitis-whooping cough-ridge ash combined vaccine, epidemic encephalitis-whooping cough-hepatitis B-each immunogenicity of antigens of ridge ash combined vaccine not interference to each other respectively.
It is emphasized that, the present invention is not to be that epidemic encephalitis, whooping cough, antigen of hepatitis B virus and inactivated poliovirus antigen are mixed into epidemic encephalitis-whooping cough combined vaccine, epidemic encephalitis-whooping cough-hepatitis B combined vaccine, epidemic encephalitis-whooping cough-hepatitis B-ridge ash combined vaccine respectively simply, but has constituted core content of the present invention according to above-mentioned 11 independent discoveries.
Combined vaccine of the present invention can reduce immune pin, reduces immune cost, increase the acceptability of vaccine, thereby enlarges immune coverage rate.
The invention provides and derive from the capsular polysaccharide in A, C, W135, the Y group meningitis cocci and derive from B group meningitis cocci outer membrane protein composite and combined vaccine that white hundred broken compositions are formed.Described polysaccharide is present in the combined vaccine with separate state or with coupling state.Described polysaccharide can be with any single composition among A, C, W135, the Y group, the perhaps various combination of two compositions, and the perhaps various combination of three compositions, perhaps the various combination of four compositions is present in the combined vaccine.Described B group meningitis cocci outer membrane protein composite is 1 valency, divalent or the multivalence outer membrane protein antigen that derives from B group meningitis cocci different shaped bacterial strain.Described white hundred broken compositions are present in the combined vaccine with full cell white hundred broken compositions or acellular white hundred broken compositions.
The invention provides to derive from the capsular polysaccharide in A, C, W135, the Y group meningitis cocci and derive from the outer membrane protein composite of B group meningitis cocci and derive from white hundred and break the combined vaccine that compositions are formed.Described polysaccharide is any single type in A, C, W135, the Y sero-group type, the perhaps various combination of two types, and the perhaps various combination of three types, perhaps the various combination of four types is present in the combined vaccine.Described outer membrane protein composite is any single type in the B sero-group type, the perhaps various combination of two types, and the perhaps various combination of three types, perhaps four types, perhaps the various combination of a plurality of types is present in the combined vaccine.Described white hundred broken compositions are present in the combined vaccine with full cell white hundred broken compositions or acellular white hundred broken compositions.
The invention provides and derive from capsular polysaccharide or the outer membrane protein in A, B, C, W135, the Y group meningitis cocci and derive from the combined vaccine that white hundred broken compositions are formed.Described polysaccharide is present in the combined vaccine with separate state or with coupling state.Described polysaccharide or outer membrane protein are to be that polysaccharide, all the other types are outer membrane protein with any single composition among A, B, C, W135, the Y group, perhaps two compositions are that polysaccharide, all the other types are outer membrane protein, and perhaps three compositions are that polysaccharide, all the other types are that outer membrane protein or four compositions are that polysaccharide, all the other types are that the various combination of outer membrane protein is present in the combined vaccine.Described white hundred broken compositions are present in the combined vaccine with full cell white hundred broken compositions or acellular white hundred broken compositions.
Meningococcus outer membrane protein of the present invention comprises following hypotype, P1.2, P1.2.5, P1.4, P1.5, P1.5.2, P1.5c, P1.5c.10, P1.7.16, P1.7.16b, P1.9, P1.15, P1.9.15, P1.12.13, P1.13, P1.14, P1.21.16, P1.22.14.
Cross reacting material in the preferred tetanus toxoid of the link coupled carrier protein of polysaccharide of the present invention (TT), diphtheria toxoid (DT), the sudden change diphtheria toxin, diphtherotoxin (CRM9, CRM197), any in the DT-Pa (PT), B group's epidemic encephalitis external membrane protein complex (OMP), epidemic encephalitis 64K outer membrane protein, hemophilus influenza P1, P2, P4, P5, P6 outer membrane protein, adhesin, reorganization Pseudomonas aeruginosa exotoxin A (rEPA), albumin, the blue albumen of spoon.
Self-existent capsular polysaccharide antigen dose is each type 1-100 μ g in the combined vaccine of the present invention, preferred 5-80 μ g, more preferably 10-60 μ g, most preferably 30-50 μ g.Coupling polysaccharide antigen dosage is each type 0.1-50 μ g, preferred 0.5-30 μ g, more preferably 1-20 μ g, most preferably 1-10 μ g.The outer membrane protein antigen dose is each type 1-100 μ g, preferred 5-80 μ g, most preferably 10-50 μ g.
Combined vaccine of the present invention also can comprise the adjuvant composition, comprises aluminium adjuvant, as aluminium hydroxide, aluminum phosphate, aluminum sulfate etc.; Oil-in-water or bacteria cell wall composition are as MF59, SAE, RAS etc.; The saponin adjuvant is as Quil A, QS-21.Bacteria lipopolysaccharide or synthetic lipoid A adjuvant; Cytokine is as interleukin, interferon, colony stimulating factor, tumor necrosis factor, costimulatory molecules B7-1, B7-2 etc.; Toxin subunit class adjuvant is as cholera toxin and subunit, pertussis toxin, PT, E.coli LT (LT) etc.
In the combined vaccine of the present invention, the vaccine dosage form comprises a kind of in liquid dosage form, freeze-dried formulation, capsule formulation, tablet, the pill, and preferred dosage form is liquid dosage form, freeze-dried formulation, capsule formulation.Can also be that partial elements is that a kind of dosage form, partial elements are another dosage form in the combined vaccine, preferred version is that partial elements is that a kind of dosage form, partial elements are another dosage form, use the associating back, more preferably scheme is that coupling or non-coupling polysaccharide are that freeze-dried formulation, DTP and/or outer membrane protein composition are liquid dosage form, in use, by liquid composition dissolving lyophilizing composition, combined immunization.
Combined vaccine route of inoculation of the present invention comprises intramuscular injection, subcutaneous injection, intradermal injection, oral, also comprises oral cavity, nasal cavity, anus, vaginal mucosa approach.
The specific embodiment
The present invention can further understand by following embodiment, and described embodiment has selected several preferred embodiments, only shows the present invention for better, but not summary of the invention is limited.
Embodiment
Embodiment 1
A group's epidemic encephalitis polysaccharide+DTP quadruple vaccine (vaccine 1)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation A group meningitis cocci polysaccharide vaccine and absorption white hundred broken combined vaccines, use with immunity after adsorbing white hundred broken combined vaccine dilution A group meningitis cocci polysaccharide vaccines.Every dosage contains 30 μ g A group meningitis cocci polysaccharide, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 2
A group's epidemic encephalitis polysaccharide+DTPa quadruple vaccine (vaccine 2)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation A group meningitis cocci polysaccharide vaccine and absorption acellular white hundred broken combined vaccines, use with immunity after adsorbing acellular white hundred broken combined vaccine dilution A group meningitis cocci polysaccharide vaccines.Every dosage contains 30 μ g A group meningitis cocci polysaccharide, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 3
A+C group's epidemic encephalitis polysaccharide+DTP pentavaccine (vaccine 3)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines,, use to adsorb white hundred broken combined vaccine dilution A+C group epidemic encephalitis polysaccharide vaccine immunity by pharmacopeia requirement preparation A+C group epidemic encephalitis polysaccharide vaccine.Every dosage contains 50 μ g A group meningitis cocci polysaccharide, contains 50 μ g C group meningitis cocci polysaccharide, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 4
A+C group's epidemic encephalitis polysaccharide+DTPa pentavaccine (vaccine 4)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines,, use to adsorb acellular white hundred broken combined vaccine dilution A+C group epidemic encephalitis polysaccharide vaccine immunity by pharmacopeia requirement preparation A+C group epidemic encephalitis polysaccharide vaccine.Every dosage contains 50 μ gA group meningitis cocci polysaccharide, contains 50 μ g C group meningitis cocci polysaccharide, and acellular white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 5
ACW135Y group's epidemic encephalitis polysaccharide+DTP seven vaccines (vaccine 5)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines,, use to adsorb white hundred broken combined vaccine dilution ACW135Y group epidemic encephalitis polysaccharide vaccine immunity by pharmacopeia requirement preparation ACW135Y group epidemic encephalitis polysaccharide vaccine.Every dosage contains 50 μ g A group meningitis cocci polysaccharide, contains 50 μ g C group meningitis cocci polysaccharide, contains 50 μ g W135 group meningitis cocci polysaccharide, contains 50 μ g Y group meningitis cocci polysaccharide, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 6
ACW135Y group's epidemic encephalitis polysaccharide+DTPa seven vaccines (vaccine 6)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, by pharmacopeia requirement preparation ACW135Y group epidemic encephalitis polysaccharide vaccine, use to adsorb acellular white hundred broken combined vaccine dilution ACW135Y group epidemic encephalitis polysaccharide vaccine immunity.Every dosage contains 50 μ g A group meningitis cocci polysaccharide, contain 50 μ g C group meningitis cocci polysaccharide, contain 50 μ g W135 group meningitis cocci polysaccharide, contain 50 μ g Y group meningitis cocci polysaccharide, acellular white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 7
A group's epidemic encephalitis combined vaccine+DTP quadruple vaccine (vaccine 7)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines, prepare A group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, use with immunity after adsorbing white hundred broken combined vaccine dilution A group epidemic encephalitis combined vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 8
A group's epidemic encephalitis combined vaccine+DTPa quadruple vaccine (vaccine 8)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, prepare A group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, use with immunity after adsorbing acellular white hundred broken combined vaccine dilution A group epidemic encephalitis combined vaccines.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 9
A+C group's epidemic encephalitis combined vaccine+DTP pentavaccine (vaccine 9)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines, prepare A group and C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, use with immunity after adsorbing white hundred broken combined vaccine dilution A groups and C group's epidemic encephalitis combined vaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ gC group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 10
A+C group's epidemic encephalitis combined vaccine+DTPa pentavaccine (vaccine 10)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, prepare A group and C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, use with immunity after adsorbing acellular white hundred broken combined vaccine dilution A groups and C group's epidemic encephalitis combined vaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 11
A+B+C group's epidemic encephalitis combined vaccine+DTP hexavaccine (vaccine 11)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines, prepare A group, B group, C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, B group's epidemic encephalitis capsular polysaccharide can use with immunity after adsorbing white hundred broken combined vaccine dilution A group, B group and C group's epidemic encephalitis combined vaccines through chemical modification.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g B group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 12
A+B+C group's epidemic encephalitis combined vaccine+DTPa hexavaccine (vaccine 12)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, prepare A group, B group, C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, B group's epidemic encephalitis capsular polysaccharide can use with immunity after adsorbing white hundred broken combined vaccine dilution A group, B group and C group's epidemic encephalitis combined vaccines through chemical modification.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g B group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 13
ACW135Y group's epidemic encephalitis combined vaccine+DTP seven vaccines (vaccine 13)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines, prepare A group, C group, W135 group and Y group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, use with immunity after adsorbing white hundred broken combined vaccine dilution ACW135Y group epidemic encephalitis combined vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 14
ACW135Y group's epidemic encephalitis combined vaccine+DTPa seven vaccines (vaccine 14)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, prepare A group, C group, W135 group and Y group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, use with immunity after adsorbing acellular white hundred broken combined vaccine dilution ACW135Y group epidemic encephalitis combined vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, acellular white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 15
ABCW135Y group's epidemic encephalitis combined vaccine+DTP eight vaccines (vaccine 15)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines, prepare A group, B group, C group, W135 group, Y group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, B group's epidemic encephalitis capsular polysaccharide can use with immunity after adsorbing white hundred broken combined vaccine dilution A groups, B group, C group, W135 group and Y group's epidemic encephalitis combined vaccine through chemical modification.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g B group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 16
ABCW135Y group's epidemic encephalitis combined vaccine+DTPa eight vaccines (vaccine 16)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, prepare A group, B group, C group, W135 group, Y group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, B group's epidemic encephalitis capsular polysaccharide can use with immunity after adsorbing acellular white hundred broken combined vaccine dilution A groups, B group, C group, W135 group and Y group's epidemic encephalitis combined vaccine through chemical modification.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, contain 5-10 μ g B group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 17
A group's epidemic encephalitis polysaccharide+DTP quadruple vaccine (vaccine 17)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparations A group meningitis cocci polysaccharide and white hundred broken each component, add or do not add adjuvant, with the lactose freeze drying protectant, the preparation freeze-dried formulation.Every dosage contains 30 μ g A group meningitis cocci polysaccharide, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 18
A group's epidemic encephalitis polysaccharide+DTPa quadruple vaccine (vaccine 18)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparations A group meningitis cocci polysaccharide and white hundred broken each component, add or do not add adjuvant, with the lactose freeze drying protectant, the preparation freeze-dried formulation.Every dosage contains 30 μ g A group meningitis cocci polysaccharide, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 19
A+C group's epidemic encephalitis polysaccharide+DTP pentavaccine (vaccine 19)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparations A group meningitis cocci polysaccharide, C group meningitis cocci polysaccharide and white hundred broken each component, add or do not add adjuvant, with the lactose freeze drying protectant, the preparation freeze-dried formulation.Every dosage contains 50 μ g A group meningitis cocci polysaccharide, contains 50 μ g C group meningitis cocci polysaccharide, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 20
A+C group's epidemic encephalitis polysaccharide+DTPa pentavaccine (vaccine 20)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparations A group meningitis cocci polysaccharide, C group meningitis cocci polysaccharide and white hundred broken each component, add or do not add adjuvant, with the lactose freeze drying protectant, the preparation freeze-dried formulation.Every dosage contains 50 μ g A group meningitis cocci polysaccharide, contains 50 μ g C group meningitis cocci polysaccharide, and acellular white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 21
ACW135Y group's epidemic encephalitis polysaccharide+DTP seven vaccines (vaccine 21)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation A group meningitis cocci polysaccharide, C group meningitis cocci polysaccharide, W135 group meningitis cocci polysaccharide, Y group meningitis cocci polysaccharide and white hundred broken each component; add or do not add adjuvant; with the lactose is freeze drying protectant, the preparation freeze-dried formulation.Every dosage contains 50 μ g A group meningitis cocci polysaccharide, contains 50 μ g C group meningitis cocci polysaccharide, contains 50 μ g W135 group meningitis cocci polysaccharide, contains 50 μ g Y group meningitis cocci polysaccharide, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 22
ACW135Y group's epidemic encephalitis polysaccharide+DTPa seven vaccines (vaccine 22)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation A group meningitis cocci polysaccharide, C group meningitis cocci polysaccharide, W135 group meningitis cocci polysaccharide, Y group meningitis cocci polysaccharide and white hundred broken each component; add or do not add adjuvant; with the lactose is freeze drying protectant, the preparation freeze-dried formulation.Every dosage contains 50 μ g A group meningitis cocci polysaccharide, contain 50 μ g C group meningitis cocci polysaccharide, contain 50 μ g W135 group meningitis cocci polysaccharide, contain 50 μ g Y group meningitis cocci polysaccharide, acellular white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 23
A group's epidemic encephalitis combined vaccine+DTP quadruple vaccine (vaccine 23)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, white hundred broken components and A group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as A group's epidemic encephalitis combined vaccine+DTP quadruple vaccine.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 24
A group's epidemic encephalitis combined vaccine+DTP quadruple vaccine (vaccine 24)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components and A group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as A group's epidemic encephalitis combined vaccine+DTP quadruple vaccine.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 25
A group's epidemic encephalitis combined vaccine+DTPa quadruple vaccine (vaccine 25)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, white hundred broken components and A group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as A group's epidemic encephalitis combined vaccine+DTP quadruple vaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 26
A group's epidemic encephalitis combined vaccine+DTPa quadruple vaccine (vaccine 26)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components and A group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as A group's epidemic encephalitis combined vaccine+DTP quadruple vaccine.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 27
A+C group's epidemic encephalitis combined vaccine+DTP pentavaccine (vaccine 27)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate and C group's conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, white hundred broken components, A group's epidemic encephalitis conjugate and C group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as A+C group's epidemic encephalitis combined vaccine+DTP pentavaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 28
A+C group's epidemic encephalitis combined vaccine+DTP pentavaccine (vaccine 28)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate and C group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components and A group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as A+C group's epidemic encephalitis combined vaccine+DTP pentavaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 29
A+C group's epidemic encephalitis combined vaccine+DTPa pentavaccine (vaccine 29)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate and C group's conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, white hundred broken components, A group's epidemic encephalitis conjugate and C group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as A+C group's epidemic encephalitis combined vaccine+DTPa pentavaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 30
A+C group's epidemic encephalitis combined vaccine+DTPa pentavaccine (vaccine 30)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate and C group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components and A group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as A+C group's epidemic encephalitis combined vaccine+DTPa pentavaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 31
A+B+C group's epidemic encephalitis combined vaccine+DTP hexavaccine (vaccine 31)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate and C group's conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, B group's capsular polysaccharide can be through modifying, white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as A+B+C group's epidemic encephalitis combined vaccine+DTP hexavaccine.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, contains 5-10 μ g B group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 32
A+B+C group's epidemic encephalitis combined vaccine+DTP hexavaccine (vaccine 32)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate and C group's conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; B group's capsular polysaccharide can be through modifying; white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as A+B+C group's epidemic encephalitis combined vaccine+DTP hexavaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g B group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 33
A+B+C group's epidemic encephalitis combined vaccine+DTPa hexavaccine (vaccine 33)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation acellular white hundred broken each component, prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate and C group's conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, B group's capsular polysaccharide can be through modifying, acellular white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as A+B+C group's epidemic encephalitis combined vaccine+DTP hexavaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g B group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 34
A+B+C group's epidemic encephalitis combined vaccine+DTPa hexavaccine (vaccine 34)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation acellular white hundred broken each component; prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate and C group's conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; B group's capsular polysaccharide can be through modifying; acellular white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as A+B+C group's epidemic encephalitis combined vaccine+DTP hexavaccine.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g B group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 35
ACW135Y group's epidemic encephalitis combined vaccine+DTP seven vaccines (vaccine 35)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, white hundred broken components, A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as ACW135Y group's epidemic encephalitis combined vaccine+DTP seven vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 36
ACW135Y group's epidemic encephalitis combined vaccine+DTP seven vaccines (vaccine 36)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components, A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as ACW135Y group's epidemic encephalitis combined vaccine+DTP seven vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 37
ACW135Y group's epidemic encephalitis combined vaccine+DTPa seven vaccines (vaccine 37)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, white hundred broken components, A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as ACW135Y group's epidemic encephalitis combined vaccine+DTPa seven vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 38
ACW135Y group's epidemic encephalitis combined vaccine+DTPa seven vaccines (vaccine 38)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components, A group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as ACW135Y group's epidemic encephalitis combined vaccine+DTPa seven vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ gY group meningitis cocci polysaccharide antigen, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 39
ABCW135Y group's epidemic encephalitis combined vaccine+DTP eight vaccines (vaccine 39)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, B group's epidemic encephalitis capsular polysaccharide can be modified, white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as ABCW135Y group's epidemic encephalitis combined vaccine+DTP eight vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g B group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ gW135 group meningitis cocci polysaccharide antigen, contain 5-10 μ gY group meningitis cocci polysaccharide antigen, white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 40
ABCW135Y group's epidemic encephalitis combined vaccine+DTP eight vaccines (vaccine 40)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as ABCW135Y group's epidemic encephalitis combined vaccine+DTP eight vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g B group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 41
ABCW135Y group's epidemic encephalitis combined vaccine+DTPa eight vaccines (vaccine 41)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component, prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed, add adjuvant, be prepared as ABCW135Y group's epidemic encephalitis combined vaccine+DTPa eight vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g B group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ gY group meningitis cocci polysaccharide antigen, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 42
ABCW135Y group's epidemic encephalitis combined vaccine+DTPa eight vaccines (vaccine 42)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation white hundred broken each component; prepare A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate and Y group's epidemic encephalitis conjugate (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method; white hundred broken components, A group's epidemic encephalitis conjugate, B group's epidemic encephalitis conjugate, C group's epidemic encephalitis conjugate, W135 group's epidemic encephalitis conjugate, Y group's epidemic encephalitis conjugate are mixed; add adjuvant; with the lactose is freeze drying protectant, and lyophilizing is prepared as ABCW135Y group's epidemic encephalitis combined vaccine+DTPa eight vaccines.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g B group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ gW135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.
Embodiment 43
ABC group's epidemic encephalitis+DTP hexavaccine (vaccine 43)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines, prepare A group and C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, prepare B group's epidemic encephalitis outer membrane protein composite (OMV) with ultrafiltration, be aided with adjuvant, be prepared into liquid or lyophilized formulations.Also above-mentioned composition can be prepared respectively, mix co-inoculation before using.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ gC group meningitis cocci polysaccharide antigen, contains 30-50 μ g B group's epidemic encephalitis outer membrane protein (OMV), and white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.Show that through the animal potency test immunogenicity of pertussis antigen is enhanced, each antigen of combined vaccine is noiseless to each other.
Embodiment 44
ABC group's epidemic encephalitis+DTPa hexavaccine (vaccine 44)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, prepare A group and C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, prepare B group's epidemic encephalitis outer membrane protein composite (OMV) with ultrafiltration, be aided with adjuvant, be prepared into liquid or lyophilized formulations.Also above-mentioned composition can be prepared respectively, mix co-inoculation before using.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contains 5-10 μ g C group meningitis cocci polysaccharide antigen, contains 30-50 μ g B group's epidemic encephalitis outer membrane protein (OMV), and acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.Show that through the animal potency test immunogenicity of pertussis antigen is enhanced, each antigen of combined vaccine is noiseless to each other.
Embodiment 45
ABCW135Y group epidemic encephalitis+DTP eight vaccines (vaccine 45)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption white hundred broken combined vaccines, prepare A group, C group, W135 group and Y group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, prepare B group's epidemic encephalitis outer membrane protein composite (OMV) with ultrafiltration, be aided with adjuvant, be prepared into liquid or lyophilized formulations.Also above-mentioned composition can be prepared respectively, mix co-inoculation before using.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ g W135 group meningitis cocci polysaccharide antigen, contain 5-10 μ g Y group meningitis cocci polysaccharide antigen, contain 30-50 μ g B group's epidemic encephalitis outer membrane protein (OMV), white hundred broken dosage are by the white hundred broken combined vaccine regulations of absorption in the pharmacopeia.Show that through the animal potency test immunogenicity of pertussis antigen is enhanced, each antigen of combined vaccine is noiseless to each other.
Embodiment 46
ABCW135Y group epidemic encephalitis+DTPa eight vaccines (vaccine 46)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines, prepare A group, C group, W135 group and Y group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, prepare B group's epidemic encephalitis outer membrane protein composite (OMV) with ultrafiltration, be aided with adjuvant, be prepared into liquid or lyophilized formulations.Also above-mentioned composition can be prepared respectively, mix co-inoculation before using.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 5-10 μ gW135 group meningitis cocci polysaccharide antigen, contain 5-10 μ gY group meningitis cocci polysaccharide antigen, contain 30-50 μ g B group's epidemic encephalitis outer membrane protein (OMV), acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.Show that through the animal potency test immunogenicity of pertussis antigen is enhanced, each antigen of combined vaccine is noiseless to each other.
Embodiment 47
Other dosage forms of combined vaccine (vaccine 47)
After various epidemic encephalitis polysaccharide composition, the lyophilizing of DTP composition, add adjuvants such as direct-connected starch, lactose, also can add the described adjuvant of description, be prepared into liquid, other outer dosage forms of freeze-dried formulation.
Embodiment 48
ABC group's epidemic encephalitis+DTPa+ hepatitis B seven vaccines (vaccine 48)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccine and hepatitis B virus vaccines, prepare A group and C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, prepare B group's epidemic encephalitis outer membrane protein composite (OMV) with ultrafiltration, be aided with adjuvant, be prepared into liquid or lyophilized formulations.Also above-mentioned composition can be prepared respectively, mix co-inoculation before using.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 30-50 μ g B group's epidemic encephalitis outer membrane protein (OMV), 5-10 μ g hepatitis B virus surface antigen, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccine regulations of absorption in the pharmacopeia.Show that through the animal potency test immunogenicity of pertussis antigen is enhanced, the immunogenicity of antigen of hepatitis B virus is enhanced, and each antigen of combined vaccine is noiseless to each other.
Embodiment 49
ABC group's epidemic encephalitis+DTPa+ deactivation ridge ash seven vaccines (vaccine 49)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccines; Make vertification regulation according to the WHO PKV and prepare deactivation purification ridge ash viral vaccine; Prepare A group and C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, prepare B group's epidemic encephalitis outer membrane protein composite (OMV), be aided with adjuvant, be prepared into liquid or lyophilized formulations with ultrafiltration.Also above-mentioned composition can be prepared respectively, mix co-inoculation before using.Every dosage contains 5-10 μ g A group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 30-50 μ g B group's epidemic encephalitis outer membrane protein (OMV), contain poliomyelitis I, II, III type virus antigen contains 10-200IU, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccines regulations of absorption in the pharmacopeia.Show that through the animal potency test immunogenicity of pertussis antigen is enhanced, the immunogenicity of ridge ash virus antigen is enhanced, and each antigen of combined vaccine is noiseless to each other.
Embodiment 50
ABC group's epidemic encephalitis+DTPa+ hepatitis B+deactivation poliomyelitis eight vaccines (vaccine 50)
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccine and hepatitis B virus vaccines; Make vertification regulation according to the WHO PKV and prepare deactivation purification ridge ash viral vaccine; Prepare A group and C group's epidemic encephalitis combined vaccine (or ammonia reducing process) with cyanogen bromide-activated, ADH derivatization method, prepare B group's epidemic encephalitis outer membrane protein composite (OMV), be aided with adjuvant, be prepared into liquid or lyophilized formulations with ultrafiltration.Also above-mentioned composition can be prepared respectively, mix co-inoculation before using.Every dosage contains 5-10 μ gA group meningitis cocci polysaccharide antigen, contain 5-10 μ g C group meningitis cocci polysaccharide antigen, contain 30-50 μ g B group's epidemic encephalitis outer membrane protein (OMV), 5-10 μ g hepatitis B virus surface antigen, contain poliomyelitis I, II, III type virus antigen contains 10-200IU, acellular white hundred broken dosage are by the acellular white hundred broken combined vaccines regulations of absorption in the pharmacopeia.Show that through the animal potency test immunogenicity of pertussis antigen is enhanced, the immunogenicity of hepatitis B antigen is enhanced, and the immunogenicity of ridge ash virus antigen is enhanced, and each antigen of combined vaccine is noiseless to each other.
Experimental example
Embodiment 1
Antibody response situation behind the combined vaccine immune mouse
According to three ones of Pharmacopoeias of People's Republic of China (version in 2005) preparation absorption acellular white hundred broken combined vaccine and hepatitis B virus vaccines; Make vertification regulation according to the WHO PKV and prepare deactivation purification ridge ash viral vaccine; According to embodiment 34,38 preparation combined vaccines.With the NIH mice of the 1/10 immune 14-18 gram of human dosage, immune 3 pins, immunity is 2 weeks at interval, and immunization route is subcutaneous, and in 1 week after the 3rd pin immunity, each antibody titer is measured in blood sampling.Assay method is selected indirect ELISA for use, and envelope antigen is selected each the univalent vaccine composition that does not add adjuvant for use.The result shows as the each component immunogenicity and is enhanced, and measurement result sees Table 1.
Embodiment 2
Combined vaccine each component immunogenicity influences each other
Adopt animal experiment to assess combined vaccine provided by the invention immunogenicity of each component after associating effect that influences each other, the immunogenicity detection method of each vaccine component is as follows in the combined vaccine:
Vaccine of epidemic menigitis immunogenicity detection method: use 1/4 dosage, by 0,14 day program immunity mice two pin, subcutaneous vaccination, in blood sampling in 28 days, separation of serum was measured the mice serum antibody titer with the ELISA method.
DPT vaccine immunogenicity detection method: carry out according to three ones of Pharmacopoeias of People's Republic of China (version in 2005).
Hepatitis b vaccination originality detection method: carry out according to three ones of Pharmacopoeias of People's Republic of China (version in 2005).
PKV immunogenicity detection method: in rat muscle injection combined vaccine, exempt from blood sampling in back 21 days, separation of serum is measured neutralization and is tired.
The result shows that combined vaccine each component immunogenicity of antigens of the present invention is not lowered after associating, be that vaccine of epidemic menigitis core and that comprise other group meningitis cocci coupling or non-coupling polysaccharide antigen does not have interference effect to pertussis antigen, diphtheria toxoid antigen, tetanus toxoid antigen, antigen of hepatitis B virus, poliovirus immunogenicity of antigens with B group meningitis cocci outer membrane protein promptly.Further show that pertussis antigen, antigen of hepatitis B virus, poliovirus immunogenicity of antigens also are reinforced after above-mentioned associating, result of the test sees Table 2 and table 3.
Figure A20081008759800291
Figure A20081008759800301
Figure A20081008759800311

Claims (15)

1, a kind of combined vaccine, it is characterized in that, described combined vaccine comprises vaccine of epidemic menigitis and DPT vaccine, wherein said vaccine of epidemic menigitis be with B group meningitis cocci outer membrane protein composite by core and comprise other group meningitis cocci and formed with a protein carrier coupling or non-link coupled polysaccharide antigen.
2, combined vaccine according to claim 1 is characterized in that, described polysaccharide antigen derives from and is selected from following one or more: a kind, 2 kinds, 3 kinds or 4 kinds of capsular polysaccharide antigens in A, C, W135, the Y group meningitis cocci.
3, combined vaccine according to claim 1, wherein said B group's outer membrane protein composite are 1 valency, divalent or the multivalence outer membrane protein composites that derives from B group meningitis cocci different shaped bacterial strain.
4, combined vaccine according to claim 2, wherein said capsular polysaccharide is to exist with a carrier protein couplet form or non-coupling form.
5, combined vaccine according to claim 4, wherein said coupling form are that polysaccharide is connected with chemical covalent bond with carrier protein, form bonding state.
6, combined vaccine according to claim 5, wherein said carrier protein are selected from cross reacting material, DT-Pa, B group's epidemic encephalitis external membrane protein complex, epidemic encephalitis 64K outer membrane protein, hemophilus influenza P1, P2, P4, P5, P6 outer membrane protein, adhesin, reorganization Pseudomonas aeruginosa exotoxin A, albumin or the blue albumen of spoon in tetanus toxoid, diphtheria toxoid, the sudden change diphtheria toxin, diphtherotoxin.
7, combined vaccine according to claim 1, wherein said white hundred broken vaccines are full cell white hundred broken vaccines or acellular white hundred broken vaccines.
8, combined vaccine according to claim 1 wherein further comprises antigen of hepatitis B virus, forms epidemic encephalitis-whooping cough-hepatitis B combined vaccine.
9, combined vaccine according to claim 1 wherein also further comprises poliovirus antigen, forms epidemic encephalitis-whooping cough-ridge ash combined vaccine.
10, the described combined vaccine of claim 1 wherein also further comprises antigen of hepatitis B virus, poliovirus antigen, forms epidemic encephalitis-whooping cough-hepatitis B-ridge ash combined vaccine.
11, according to claim 1,8,9,10 each described combined vaccines, wherein various compositions are sub-packed in respectively in each autonomous container, when immunity, mix inoculating; Or several compositions are prepared into independent vaccine, mix inoculating when immunity; Or just be sub-packed in the preparation in the container and become multiple vaccines.
12, according to claim 1,8,9,10 each described combined vaccines, wherein this combined vaccine is any in liquid dosage form, freeze-dried formulation, capsule formulation, tablet, the pill or several.
13, according to claim 1,8,9,10 each described combined vaccines, wherein this combined vaccine further comprises aluminum salt adjuvant and other adjuvants.
14, combined vaccine according to claim 13, wherein said aluminum salt adjuvant is selected from aluminium hydroxide, aluminum sulfate or aluminum phosphate.
15, according to claim 1,8,9,10 each described combined vaccines, wherein this combined vaccine is to carry out immunity by being selected from following mode: injection, the spraying of oral, mucosa or place.
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