CN101708331A - Novel human rabies vaccine and method for preparing same - Google Patents
Novel human rabies vaccine and method for preparing same Download PDFInfo
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- CN101708331A CN101708331A CN200910177427A CN200910177427A CN101708331A CN 101708331 A CN101708331 A CN 101708331A CN 200910177427 A CN200910177427 A CN 200910177427A CN 200910177427 A CN200910177427 A CN 200910177427A CN 101708331 A CN101708331 A CN 101708331A
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Abstract
The invention relates to novel human rabies vaccine and a method for preparing the same, mainly aiming at overcoming the defects that the prior human rabies vaccine needs to have a certain amount of antigen needed by the effective antibodies, has poor stability and generates effective antibody with nonideal strength. The novel human rabies vaccine comprises human rabies purified stock solution and tetanus toxoid which are prepared with the conventional method, wherein the tetanus toxoid has the effect of rapidly enhancing the immunity to the inactivated rabies virus. The novel human rabies vaccine can achieve better immune effect by using fewer antigens. The novel human rabies vaccine is prepared in the earlier stage with the prior production process of the human rabies purified stock solution and the prior production process of the tetanus toxoid and in the later stage by mixing the human rabies purified stock solution and the tetanus toxoid according to the certain proportion of the amount of the contained antigens. The novel human rabies vaccine can be directly used for preventing the rabies virus and the clostridium tetanus and can achieve the effect of the combined vaccine.
Description
Two. affiliated field
The present invention relates to the Antirabic Vaccine and preparation method
Three. background technology (early stage document or list of references)
Rabies (rabies) have another name called hydrophobia (hydrophobia), are a kind of acute infectious disease that is caused by rabies virus infection.Main rabies virus host is animals such as wolf, Vulpes, dog.Rabies still do not have active drug and can treat, in case 100% death of falling ill.But can prevent by inoculation rabies vaccine or injection antiserum
1.
Rabies worldwide all have generation and popular, according to having 87 countries (not containing China) to have rabies in 156 countries of WHO data (Bogel1986) statistics, as India, Thailand, Tunisia, Brazil, Ethiopia, Salvador etc. all is the hotspot, and India dies from about 10000～20000 examples of rabic case every year.The eighties in 20th century, China is only second to India and occupies the second place of the world
2.Since the founding of New, actively developed rabic preventing and controlling, at present basic controlling the human world popular.
Rabies vaccine is to prevent rabies that unique effective medicine takes place at present, mostly the used vaccine in various countries is cell vaccine now, comprises purification hamster kidney cell rabies vaccine, purification Vero cell rabies, human diploid cell rabies vaccine, purification chick-embryo cell rabies vaccine etc.The used vaccine of a very long time China is to be the vaccine of adjuvant with the aluminium hydroxide; but because there is the effect of slow release in aluminum hydroxide adjuvant; (14 days～21 days) produce effectively protection antibody in a short time; present Antirabic Vaccine is the vaccine of no adjuvant; but there is not the no adjuvant rabies virus of aluminium hydroxide absorption very unstable; in the preservation process, need to add the human albumin as protective agent, increased the vaccine cost.
Do not have the adjuvant Antirabic Vaccine in addition and need reach the required antigen amount height of potent antibodies, poor stability, the potent antibodies intensity that produces is undesirable, at present the quality control aspect of rabies vaccine is strengthened day by day, the strictness of DNA residual quantity and total protein content control certainly will require in the future that prepared Antirabic Vaccine has low antigen amount, and height is tired, can produce potent antibodies fast, so the development new generation vaccine becomes the emphasis of research.
Four. summary of the invention (contents of a project)
An object of the present invention is to provide a kind of novel Antirabic Vaccine, it contains the human rabies purification stock solution and the tetanus toxoid of conventional method preparation, tetanus toxoid has the effect of quick enhance immunity to the rabies virus of deactivation, the novel human rabies vaccine of development can produce the neutralizing antibody of effective high titre fast in 7 days, reach the effect that obtains senior middle school and antibody in a short time, and neutralizing antibody is held time longer, patient for mad dog severe is bitten and incubation period is short provides a kind of safer and more effective Antirabic Vaccine.
Another object of the present invention is to reduce human rabies purification stock solution antigen amount, uses antigen amount seldom to reach good immune effect exactly.Antigenic the yielding poorly of human rabies purification stock solution, the preparation cost height the invention provides a kind of production method of novel human rabies vaccine, may further comprise the steps.
1, prepares human rabies purification stock solution and tetanus toxoid respectively with conventional method.
2, these two kinds of compositions are mixed by a certain percentage;
3, mixed vaccine is carried out packing or lyophilizing by liquid dosage form vaccine and freeze-dried formulation vaccine;
4, the product after the packing is packed after the finished product calibrating, promptly obtained required novel human rabies vaccine.
Said two kinds of compositions by the mixed proportion of antigenic content are: 1/3～2/3 of human rabies purification stock solution constant: the consumption of tetanus toxoid is 3Lf/ agent～10Lf/ agent.
Production method of the present invention, utilize the production technology of existing rabies purification stock solution production technology and tetanus toxoid early stage, later stage is carried out hybrid combination by contained antigen amount certain proportion, obtain novel human rabies vaccine, reduce rabies purification stock solution antigen amount thereby reach, reduce stabilizing agent such as human albumin's use, improve the quality of products, improve vaccine valence, the effect of enhance immunity.
The 3rd purpose of the present invention just provides a kind of novel human rabies vaccine, the effect that not only has the prevention rabies virus, and the effect that can also prevent clostridium tetanus to infect, after mad dog severe is bitten, need inject a large amount of tetanus antitoxin in addition usually, have bigger untoward reaction; Use novel human rabies vaccine can directly prevent rabies virus and clostridium tetanus, reach the effect of combined vaccine.
Five. description of drawings (if drawings attached)
Fig. 1 uses the neutralizing antibody of different 5 vaccines of the present invention of joining.
Fig. 2 shows the comparative result with traditional vaccine of tiring of vaccine of the present invention.
Fig. 3 shows the immune effect that uses vaccine of the present invention
Six. specific embodiments (or method)
Embodiment 1:
Respectively get human rabies purification stock solution (hamster kidney cell) (production of Fu Er bio-pharmaceuticals limited company), tetanus toxoid stock solution (production of Fu Er bio-pharmaceuticals limited company), dilution is the vaccine of 1 dosage, 1/2 dosage according to the antigen amount, and aqueous vaccine is made in combination respectively.In the experimentation, establish independent Antirabic Vaccine and be matched group, measure tiring of four kinds of combination-vaccines respectively according to the method for three ones of Chinese Pharmacopoeias.Experimental result such as Fig. 2-1.By among Fig. 2-1 as seen, the tiring of rabies vaccine (6.32IU/mL) of adding 7Lf unit's tetanus toxoid increases 2.5IU/mL than tire (3.74IU/mL) of matched group; Tire (3.77IU/mL) of the vaccine that 7Lf unit's tetanus toxoid and 1/2 dosage rabies purification stock solution antigen are formed tires (3.74IU/mL) greater than matched group, and the tiring of the vaccine of 3.5Lf unit's tetanus toxoid and 1/2 dosage rabies purification stock solution antigen composition (3.15IU/mL) is a little less than matched group tire (3.74IU/mL).Therefore this description of test tetanus toxoid can obviously increase the effect of tiring of rabies vaccine, plays the effect of enhance immunity; In the preparation of vaccine, can significantly reduce human rabies purification stock solution antigen amount.
Embodiment 2:
Respectively get human rabies purification stock solution (VERO cell) (production of Fu Er bio-pharmaceuticals limited company), tetanus toxoid stock solution (production of Fu Er bio-pharmaceuticals limited company), dilution is the vaccine of 1 dosage, 1/2 dosage according to the antigen amount, and aqueous vaccine is made in combination respectively.In the experimentation, establish the Antirabic Vaccine and be matched group, measure tiring of four kinds of combination-vaccines respectively according to the method for three ones of Chinese Pharmacopoeias.Experimental result such as Fig. 2-2.By among Fig. 2-2 as seen, the tiring of rabies vaccine (6.48IU/mL) of adding 7Lf unit's tetanus toxoid increases 2.63IU/mL than tire (3.85IU/mL) of matched group; Tire (3.90IU/mL) of the vaccine that 7Lf unit's tetanus toxoid and 1/2 dosage rabies purification stock solution antigen are formed tires (3.85IU/mL) greater than matched group, and tire (3.80IU/mL) of 3Lf unit's tetanus toxoid and the vaccine of 1/2 dosage rabies purification stock solution antigen composition is equivalent to matched group tire (3.85IU/mL).Therefore this description of test tetanus toxoid can obviously increase the effect of tiring of rabies vaccine, plays the effect of enhance immunity; In the preparation of vaccine, can significantly reduce human rabies purification stock solution antigen amount.
Embodiment 3:
Respectively get human rabies purification stock solution (diploid cell) (production of Fu Er bio-pharmaceuticals limited company), tetanus toxoid stock solution (production of Fu Er bio-pharmaceuticals limited company), dilution is the vaccine of 1 dosage, 1/2 dosage according to the antigen amount, and aqueous vaccine is made in combination respectively.In the experimentation, establish the Antirabic Vaccine and be matched group, measure tiring of four kinds of combination-vaccines respectively according to the method for three ones of Chinese Pharmacopoeias.Experimental result such as Fig. 2-3.By among Fig. 2-3 as seen, the tiring of rabies vaccine (6.80IU/mL) of adding 7Lf unit's tetanus toxoid increases 2.55IU/mL than tire (4.25IU/mL) of matched group; Tire (4.45IU/mL) of the vaccine that 7Lf unit's tetanus toxoid and 1/2 dosage rabies purification stock solution antigen are formed tires (4.25IU/mL) greater than matched group, and tire (4.05IU/mL) of 3.5Lf unit's tetanus toxoid and the vaccine of 1/2 dosage rabies purification stock solution antigen composition is equivalent to matched group tire (4.25IU/mL).Therefore this description of test tetanus toxoid can obviously increase the effect of tiring of rabies vaccine, plays the effect of enhance immunity; In the preparation of vaccine, can significantly reduce human rabies purification stock solution antigen amount.
Embodiment 4:
Respectively get human rabies purification stock solution (hamster kidney cell) (production of Fu Er bio-pharmaceuticals limited company), tetanus toxoid stock solution (production of Fu Er bio-pharmaceuticals limited company), dilution is the vaccine of 1 dosage, 1/2 dosage according to the antigen amount, and aqueous vaccine is made in combination respectively.In the experimentation, establish the Antirabic Vaccine and be matched group, wherein only adding 1% human albumin in matched group is protective agent, and after 14 days, the heat of measuring four kinds of combination-vaccines according to the method for three ones of Chinese Pharmacopoeias respectively is steady 37 ℃ of placements.The heat that experimental results show that the rabies vaccine of adding 7Lf unit's tetanus toxoid surely tire (4.80IU/mL) than the heat of matched group surely tire (2.75IU/mL) increase 2.05IU/mL; The heat of the vaccine that 7Lf unit's tetanus toxoid and 1/2 dosage rabies purification stock solution antigen are formed surely tire (2.95IU/mL) surely tire (2.75IU/mL) greater than matched group heat, 3.5Lf unit's tetanus toxoid and the heat of the vaccine of 1/2 dosage rabies purification stock solution antigen composition surely tire (2.65IU/mL) be equivalent to matched group heat surely tire (2.75IU/ml).Therefore this description of test tetanus toxoid can not only obviously increase the effect of tiring of rabies vaccine, plays the effect of enhance immunity; And can replace the human albumin and play the antigenic effect of protection, reduce cost.
Embodiment 5:
Respectively get human rabies purification stock solution (hamster kidney cell) (production of Fu Er bio-pharmaceuticals limited company), tetanus toxoid stock solution (production of Fu Er bio-pharmaceuticals limited company), dilution is the vaccine of 1 dosage, 1/2 dosage according to the antigen amount, and aqueous vaccine is made in combination respectively.In the experimentation, establish the Antirabic Vaccine and be matched group, wherein only adding 1% human albumin in matched group is protective agent, carries out the specificity of four kinds of combination-vaccines according to the method for three ones of Chinese Pharmacopoeias respectively and tests unusually.Experimental result is all qualified.Illustrate that the new semple type rabies vaccine that adds tetanus toxoid is safe, effectively.
Embodiment 6:
With the vaccine of 4 kinds of combinations of above-mentioned case combination immune mouse respectively, each immune 0.5ml, immunity 2 times respectively in 0 day, 7 days respectively blood sampling in 7,14,21,28 days, detects the serum neutralizing antibody and tires.Experimental result such as Fig. 1, Fig. 3.As seen from Figure 1, the new semple type rabies vaccine of the tetanus toxoid that all interpolations are not commensurability has all produced the neutralizing antibody of high titre in the time of 7 days, the neutralizing antibody that adds the rabies vaccine of 7Lf unit's tetanus toxoid is 30.23IU/ml, be far longer than matched group (Antirabic Vaccine) 0.83IU/ml, the serum neutralizing antibody improves about 36 times; After immunity 14 days, all serum NATs that add the new semple type rabies vaccine generation of not commensurability tetanus toxoid maintain high level, especially the antibody titer of the vaccine of 3.5Lf unit's tetanus toxoid and 1/2 dosage rabies purification stock solution antigen composition increases to 21.4IU/ml fast, and the neutralizing antibody of matched group has only 0.96IU/ml; After immunity 21 days, all serum NATs that add the new semple type rabies vaccine generation of not commensurability tetanus toxoid still maintain high level, NAT is 5～15IU/ml, and the neutralizing antibody of matched group drops to about 0.13IU/ml, well below effective protection antibody 0.5IU/ml; The serum neutralizing antibody on average improves about 50～150 times; After immunity 28 days, though all serum neutralizing antibodies that add the new semple type rabies vaccine generation of not commensurability tetanus toxoid descend to some extent, but the serum neutralizing antibody still is far longer than the requirement of effective neutralizing antibody 0.5IU/ml, NAT is 4～10IU/ml, and the NAT of matched group drops to 0.09IU/ml.Therefore this experiment proves absolutely that the novel human rabies vaccine of development can produce the neutralizing antibody of effective high titre fast in 7 days, reach the effect that obtains senior middle school and antibody in a short time, and the persistent period of neutralizing antibody is longer, patient for mad dog severe is bitten and incubation period is short provides a kind of safer and more effective Antirabic Vaccine.The effect of the novel human rabies vaccine of development is significant, will play important effect in rabic control.
Claims (7)
1. a novel human rabies vaccine is characterized in that being made up of human rabies purification stock solution and tetanus toxoid.
2. human rabies purification stock solution according to claim 1 is meant the human rabies purification stock solution by hamster kidney cell tissue culture or diploid cell cultivation or Vero cell culture or the preparation of chick-embryo cell culture purified.
3. tetanus toxoid according to claim 1 is meant the tetanus toxoid by traditional method or gene engineering method preparation.
4. the consumption according to claim 1,2 described human rabies purification stock solutions is 1/3～2/3 of a constant.
5. the consumption according to claim 1,3 described tetanus toxoid is 3Lf/ agent～10Lf/ agent.
6. measure according to the optimum selection human rabies purification stock solution 1/3 of claim 1,4,5 described human rabies purification stock solutions and tetanus toxoid: tetanus toxoid 3LF; Human rabies purification stock solution 1/2 amount: tetanus toxoid 4LF.
7. Antirabic Vaccine according to claim 1 can be that not add human albumin etc. protectant.
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| CN200910177427A CN101708331A (en) | 2009-09-29 | 2009-09-29 | Novel human rabies vaccine and method for preparing same |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102671194A (en) * | 2012-05-07 | 2012-09-19 | 成都康华生物制品有限公司 | Human vaccine for preventing hydrophobia and tetanus |
| CN103374070A (en) * | 2012-04-24 | 2013-10-30 | 中国科学院上海生命科学研究院 | Anti-rabies-virus combination molecule 2F5 |
| CN114470184A (en) * | 2021-12-30 | 2022-05-13 | 孙嘉玮 | Combined vaccine for tetanus, canine distemper and rabies for livestock |
-
2009
- 2009-09-29 CN CN200910177427A patent/CN101708331A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103374070A (en) * | 2012-04-24 | 2013-10-30 | 中国科学院上海生命科学研究院 | Anti-rabies-virus combination molecule 2F5 |
| CN103374070B (en) * | 2012-04-24 | 2016-01-27 | 中国科学院上海生命科学研究院 | A kind of binding molecule 2F5 of rabies poison |
| CN102671194A (en) * | 2012-05-07 | 2012-09-19 | 成都康华生物制品有限公司 | Human vaccine for preventing hydrophobia and tetanus |
| CN114470184A (en) * | 2021-12-30 | 2022-05-13 | 孙嘉玮 | Combined vaccine for tetanus, canine distemper and rabies for livestock |
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Open date: 20100519 |