CN101541343A - Use of clostridium perfringens type C bacterium for the manufacture of a vaccine - Google Patents
Use of clostridium perfringens type C bacterium for the manufacture of a vaccine Download PDFInfo
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- CN101541343A CN101541343A CNA2007800427077A CN200780042707A CN101541343A CN 101541343 A CN101541343 A CN 101541343A CN A2007800427077 A CNA2007800427077 A CN A2007800427077A CN 200780042707 A CN200780042707 A CN 200780042707A CN 101541343 A CN101541343 A CN 101541343A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
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Abstract
The present invention relates to the use of Clostridium perfringens type C bacterium for the manufacture of a vaccine.
Description
The present invention relates to the purposes that C type bacillus perfringens (Clostridium perfringens) is used to prepare vaccine.
Clostridium is the gram-positive anaerobic bacterium that forms spore.It is the pathogen of domestic animal and wild animal that clostridium is widely acknowledged to be.Songer, J.G.in The Clostridia; Chapter10:Clostridial Diseases of Animals, Molecular biology andPathogenesis, ed.Rood, J.I.et al., Academic Press Ltd (1997) ISBN0-12-595020-9 have summarized the Animal diseases that various clostridiums and they cause.
In present known clostridial species, bacillus perfringens is considered to the bacterial pathogens of extensive existence sometimes, and in all clostridial species, it is the most important reason of clostridium enteropathy in the domestic animal without doubt.
Based on the main toxin that they produce, the bacillus perfringens kind is divided into five kinds of types, A-E type again.
A and C type bacillus perfringens, with clostridium difficile be the main intestinal clostridial disease substance of pig.
Songer, J.G. and Uzal, F.A. (J.Vet.Diagn.Invest17:528-536 (2005)) have specifically described the clostridium intestinal in the pig and have infected.
C type bacillus perfringens infected pigs, cattle, chicken, people, sheep, Canis familiaris L. and horse.The easiest C of the being subjected to type of piglet bacillus perfringens infects.In the biggest piglet of 1-2, this infection has caused the sickness rate of 30%-50% and has caused the mortality rate of 50%-100%.Bigger piglet (1-2 age in week) may have long course of infection.
Sow is the generally source of infecting.
The common method of protection piglet is with C type bacillus perfringens vaccination sow, to induce the antibody that can pass to their offspring by colostrum.This causes when piglet is subject to the clostridium infection most, to the high-caliber protection of piglet.This vaccine is based on toxoid.Usually, they are detoxified supernatant vaccines, wherein do not have cell.Springer, S. and Selbitz, H.-J. (FEMS Immum.and Medical Microbiol.24:333-336 (1999)) has described toxoid vaccine.
A type bacillus perfringens infects lambs, goat, calf, chicken, pig, horse, Canis familiaris L. and people.In the pig that reaches full growth, A type bacillus perfringens is the member of normal intestinal flora.Therefore suppose the adverse effect that the pig that reaches full growth is not existed by enteral A type bacillus perfringens at present.But it may new life with the wean pig in cause the pig necrotizing enterocolitis.Be used to protect pig seldom to the vaccine of anti-A type bacillus perfringens.A kind of commerce obtainable (ratifying conditionally) vaccine is only arranged at present.
One of reason of this situation may be that as mentioned above, A type bacillus perfringens is the member's of normal flora the fact.Therefore, people can not expect its triggering immune system.Therefore, people can not expect to induce the antibody to the anti-A type bacillus perfringens to produce.If induced antibody, A type bacillus perfringens will can not survive in the intestinal, let alone be the member of normal flora.Therefore, further, people expect that surely not sow transmits any protection by colostrum and given their offspring.No matter as if owing to what reason, A type bacillus perfringens can not be induced enough immunostimulations.
Find surprisingly that at present the C type bacillus perfringens vaccine that comprises the culture supernatants of detoxification can be induced the cross protection that the anti-A type bacillus perfringens is infected very much.
More surprisingly, find to cause their piglet the remarkable protection of anti-A type bacillus perfringens infection with C type bacillus perfringens culture supernatants vaccination of sows.
More surprisingly, discovery even sow also show better later in this vaccination.This is surprising, because as mentioned above, and general hypothesis, the adverse effect that pig that reaches full growth such as sow are not infected by A type bacillus perfringens.This finds to have proved for the first time opposite situation.
Therefore, first embodiment of the present invention relates to the application that C type bacillus perfringens is used to prepare vaccine, and this vaccine is used to protect the pig that reaches full growth that the anti-A type bacillus perfringens is infected.
Second embodiment of the present invention relates to the application that C type bacillus perfringens is used to prepare vaccine, and this vaccine is used to protect sow that the anti-A type bacillus perfringens is infected.
The 3rd embodiment of the present invention relates to the application that C type bacillus perfringens is used to prepare the vaccine that is used for sow, and this vaccine is used to protect piglet that the anti-A type bacillus perfringens is infected.
The 4th embodiment of the present invention relates to the application that C type bacillus perfringens is used to prepare vaccine, and this vaccine is used to protect piglet that the anti-A type bacillus perfringens is infected.
Because it will be appreciated by those skilled in the art that, in fact, the application that C type bacillus perfringens is used for preparing vaccine is the process in one two step: C type bacillus perfringens is used for growing in culture medium, and to obtain culture supernatants, it is the basis that is used to prepare vaccine of the present invention.
Therefore, another embodiment of the invention relates to the application that C type bacillus perfringens culture supernatants is used to prepare vaccine, and this vaccine is used to protect the pig that reaches full growth that the anti-A type bacillus perfringens is infected.
Remain another embodiment of the invention, relate to the application that C type bacillus perfringens culture supernatants is used to prepare vaccine, this vaccine is used to protect sow that the anti-A type bacillus perfringens is infected.
Be again another embodiment of the invention, relate to the application that C type bacillus perfringens culture supernatants is used to prepare the vaccine that is used for sow, this vaccine is used to protect piglet that the anti-A type bacillus perfringens is infected.
Still one embodiment of the invention relate to the application that C type bacillus perfringens culture supernatants is used to prepare vaccine, and this vaccine is used to protect piglet that the anti-A type bacillus perfringens is infected.
Between C type clostridium perfringens toxoid type, can and not produce between those bacterial strains of β-2 toxin at those bacterial strains that produce β-2 toxin and distinguish.About 40% produces this toxin in all C type bacillus perfringens bacterial strains.
Find that the C type bacillus perfringens that produces β-2 toxin is more suitable for than the C type bacillus perfringens that does not produce β-2 toxin.Fisher, people such as D.J. (Inf.﹠amp; Immun.74:5200-5210 (2006)) this bacterial strain and their evaluation have been described.
Therefore, a preferred form of this embodiment relates to a kind of application, wherein uses the C type bacillus perfringens that produces β-2 toxin.
Zhi Bei vaccine is administered to unique vaccine of pig anything but in the swine rearing process of industry as mentioned above.About vaccine with swine diseases protozoa of resisting other and virus provides clostridial vaccine simultaneously through being everlasting.
Therefore, in another preferred embodiment, the vaccine for preparing described in the present invention comprises that in addition one or more derive from the antigen of swine diseases protozoa or virus, anti-those the antigenic antibody or this antigenic hereditary information of encoding.
This organism or virus preferably are selected from pseudorabies virus, PRRS virus, swine influenza virus, pig parvoviral, transmissible gastro-enteritis virus, rotavirus, escherichia coli, erysipelothrix ruhsiopathiae, bordetella bronchiseptica, salmonella typhimurium, Salmonella choleraesuls, haemophilus parasuis, pasteurella multocida, Streptococcus suis, Mycoplasma hyopneumoniae, short spirillum of swine dysentery and Actinobacillus pleuropneumoniae.
Therefore, a kind of more preferred form of this embodiment relates to a kind of vaccine for preparing described in the present invention, it comprises that in addition one or more derive from the antigen of swine diseases protozoa or virus, and wherein these organisms or virus are selected from pseudorabies virus, PRRS virus, swine influenza virus, pig parvoviral, transmissible gastro-enteritis virus, rotavirus, escherichia coli, erysipelothrix ruhsiopathiae, bordetella bronchiseptica, salmonella typhimurium, Salmonella choleraesuls, haemophilus parasuis, pasteurella multocida, Streptococcus suis, Mycoplasma hyopneumoniae, short spirillum of swine dysentery and Actinobacillus pleuropneumoniae.
And then after bacillus perfringens infected, piglet often suffered coli-infection.Escherichia coli are reasons of another kind of serious intestinal tract disease in the piglet.Therefore, through bacillus coli vaccine inoculation piglet commonly used or in-pig.Bacillus coli vaccine is generally used for this area, and they are commercially available.Therefore, the combination-vaccine of a kind of C of comprising type bacillus perfringens culture supernatants and bacillus coli vaccine component is very desirable, because it can prevent C type bacillus perfringens, A type bacillus perfringens and coli-infection.
Therefore, a kind of most preferred form of this embodiment relates to a kind of vaccine for preparing described in the present invention, and it comprises in addition and derives from colibacillary one or more antigens of swine diseases protozoa.
With non-limiting way the present invention is illustrated in the following embodiments.
Embodiment
The antigenic generation of C type bacillus perfringens
With the C type bacillus perfringens bacterial strain of a strain standard, bacterial strain 587 (being also referred to as CWC 1/S, from Weybridge U.K.Collection) is incubated in the fermentation tank and begins up to stationary growth phase.Centrifugal culture abandons the precipitation that comprises bacterial cell.Add formaldehyde final concentration to 0.5%v/v in the supernatant,, then filter and concentrate by ultrafiltration and 0.2 μ m with the deactivation toxin.
Vaccine production
By mixed C type bacillus perfringens antigen with prepare vaccine based on the adjuvant of tocopherol.Each vaccine dose (2ml) comprises 17 times of spissated C type bacillus perfringens Antigens toxin culture supernatants concentrate of 20 μ l.This vaccine is abideed by about the European Pharmacopoeia monograph 0363 of the safety and the effectiveness of C type vaccine (the bacillus perfringens vaccine is used for the veterinary and uses).
In addition, in this experiment, add the bacillus coli antigen (F4ab, F4ac, F5 and F6 cilium and thermolabile toxin) of purification, to suppress possible coli-infection.These components are known in the art, and one skilled in the art will know that the vaccine that how to prepare based on these components.
As selection, but those skilled in the art can use the commercially available and ready-made bacillus coli vaccine that can use, and (can pass through IntervetInt.B.V., Wim de Korverstraat 35 as Porcilis Porcoli DF, Boxmeer, The Netherlands obtains).
Control vaccine comprises identical component, and except that C type bacillus perfringens antigen, it is not present in the matched group.
The protection of sow
A guinea pig production farm, wherein once once clinical A type bacillus perfringens outburst is selected for randomization double blinding drug efficacy study on the spot.Find to separate and produce alpha-toxin and β 2-toxin from the A on this farm type bacillus perfringens.
Phenolics, in about 6 to 2 weeks before the farrowing, sow is with the vaccine (matched group) that only comprises bacillus coli antigen or with comprising bacillus coli antigen and the antigenic vaccine of C type bacillus perfringens (test group) IM inoculation.Vaccine is with different color marks (2x test vaccine, 1x control vaccine), guaranteeing double blinding, and being assigned as of sow about 2: 1 (table 1) in two groups.
Table 1. group size
| Group | The sow number | The piglet number alive of every sow birth | The sum of piglet |
| Contrast | 41 | 11.6 | 453 |
| Test | 77 | 12.1 | 904 |
From first time vaccination same day when the weaned piglet (3-4 week after the farrowing), observed general health, feed intake and the diarrhoea of sow in per 3 days.For the ease of statistical analysis, used clinical marking system (table 2).Between the period 1 of life, observe the piglet of the sow have an instinct for inoculation every day, from a week up to per three days of wean once, after this finish up to the nurse phase once in a week.The record general health, feed intake, diarrhoea and mortality rate (table 2).
Table 2 is used for the marking system of sow and piglet:
| Clinical scores | Behavior | Appetite | The denseness of feces | Feces is formed |
| 0 | Normally | Normally | Normally | Normally |
| 1 | Depressed | Slight inappetence | Soft | There is mucus |
| 2 | Lethargy | Tangible inappetence | Liquid | The mucus that has band blood |
| 3 | Dying | Do not suck | Water sample | There are blood and intestinal cast |
The result
The clinical observation of table 3. sow
Table 3 has shown compared to not containing the antigenic vaccination of C type bacillus perfringens, has used the influence that comprises the antigenic vaccination of C type bacillus perfringens.
As drawing, with comprising the improvement that the antigenic vaccination of C type bacillus perfringens causes sow health status highly significant from table 3 is clear.
The offspring's of vaccination of sows protection
Equally, will compare with the mortality rate in the littermate of the sow that comprises the antigenic vaccination of C type bacillus perfringens and with the mortality rate in the littermate of the sow that does not contain the antigenic vaccination of C type bacillus perfringens.
As drawing, significantly be lower than matched group with the mortality rate in the littermate of the sow that comprises the antigenic vaccination of C type bacillus perfringens from table 4 is clear.
In addition, table 5 shows to come the personal piglet that comprises the sow of the antigenic vaccination of C type bacillus perfringens to have the clinical scores that significantly is lower than matched group.
Mortality rate weekly in table 4. contrast and the test littermate
| Age (my god) | Contrast | Test |
| 0-6 | 29 | 22 |
| 7-13 | 3 | 3 |
| 14-21 | 7 | 2 |
| 21-27 | 6 | 1 |
| 28-34 | 2 | 1 |
| 35-41 | 0 | 0 |
| 42-48 | 1 | 1 |
| 49-55 | 1 | 1 |
| 56-62 | 1 | 0 |
| 63-70 | 0 | 0 |
| Amount to (%) | 50(11.04) | 31(3.43) |
The clinical observation of table 5. piglet
Conclusion: data show, cause when facing the outburst of A type bacillus perfringens with comprising the antigenic vaccination sow of C type bacillus perfringens, and the sow of inoculation and their offspring's health status are improved significantly.
Claims (12)
1) C type bacillus perfringens is used to prepare the application of vaccine, and this vaccine is used to protect the pig anti-A type bacillus perfringens that reaches full growth to infect.
2) C type bacillus perfringens is used to prepare the application of vaccine, and this vaccine is used to protect sow anti-A type bacillus perfringens to infect.
3) C type bacillus perfringens is used to prepare the application of the vaccine that is used for sow, and this vaccine is used to protect piglet anti-A type bacillus perfringens to infect.
4) C type bacillus perfringens is used to prepare the application of vaccine, and this vaccine is used to protect piglet anti-A type bacillus perfringens to infect.
5) the C type bacillus perfringens culture supernatants application that is used to prepare vaccine, this vaccine are used to protect the pig anti-A type bacillus perfringens that reaches full growth to infect.
6) the C type bacillus perfringens culture supernatants application that is used to prepare vaccine, this vaccine are used to protect sow anti-A type bacillus perfringens to infect.
7) the C type bacillus perfringens culture supernatants application that is used to prepare the vaccine that is used for sow, this vaccine are used to protect piglet anti-A type bacillus perfringens to infect.
8) the C type bacillus perfringens culture supernatants application that is used to prepare vaccine, this vaccine are used to protect piglet anti-A type bacillus perfringens to infect.
9) application of claim 1-8 is characterized in that using the C type bacillus perfringens that produces β-2 toxin.
10) application of claim 1-9 is characterized in that other one or more derive from the antigen of swine diseases protozoa or virus, and anti-those the antigenic antibody or this antigenic hereditary information of encoding are used to prepare described vaccine.
11) application of claim 10 is characterized in that described causal organism or virus are selected from pseudorabies virus, PRRS virus, swine influenza virus, pig parvoviral, transmissible gastro-enteritis virus, rotavirus, escherichia coli, erysipelothrix ruhsiopathiae, bordetella bronchiseptica, Salmonella choleraesuls, salmonella typhimurium, haemophilus parasuis, pasteurella multocida, Streptococcus suis, Mycoplasma hyopneumoniae, short spirillum of swine dysentery and Actinobacillus pleuropneumoniae.
12) application of claim 10 is characterized in that described swine diseases protozoa is escherichia coli.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86044706P | 2006-11-20 | 2006-11-20 | |
| EP06124404 | 2006-11-20 | ||
| EP06124404.2 | 2006-11-20 | ||
| US60/860,447 | 2006-11-20 | ||
| PCT/EP2007/062484 WO2008061950A1 (en) | 2006-11-20 | 2007-11-19 | Use of clostridium perfringens type c bacterium for the manufacture of a vaccine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101541343A true CN101541343A (en) | 2009-09-23 |
| CN101541343B CN101541343B (en) | 2012-05-16 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007800427077A Expired - Fee Related CN101541343B (en) | 2006-11-20 | 2007-11-19 | Use of clostridium perfringens type c bacterium for the manufacture of a vaccine |
Country Status (8)
| Country | Link |
|---|---|
| CN (1) | CN101541343B (en) |
| AT (1) | ATE540692T1 (en) |
| BR (1) | BRPI0718639A2 (en) |
| DK (1) | DK2086578T3 (en) |
| ES (1) | ES2380134T3 (en) |
| RU (1) | RU2462263C2 (en) |
| TW (1) | TWI369991B (en) |
| UA (1) | UA95652C2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107789622A (en) * | 2017-10-18 | 2018-03-13 | 山东农业大学 | A kind of calf enterotoxemia C.perfringens β2The preparation method of toxin toxoid vaccine |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102688484B (en) * | 2012-06-13 | 2016-03-30 | 北京中海生物科技有限公司 | A kind of production method of chicken necrotizing enterocolitis (C type) inactivated vaccine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2129441C1 (en) * | 1997-12-10 | 1999-04-27 | Пирожков Михаил Константинович | Mixed vaccine against anaerobic enterotoxemia and escherichiosis in piglets |
| UA65816A (en) * | 2003-05-30 | 2004-04-15 | Vasyl Petrovych Ryzhenko | Vaccine velshisan for preventing toxicoinfections caused by clostridium perfringens |
-
2007
- 2007-10-26 TW TW096140460A patent/TWI369991B/en not_active IP Right Cessation
- 2007-11-19 DK DK07822693.3T patent/DK2086578T3/en active
- 2007-11-19 AT AT07822693T patent/ATE540692T1/en active
- 2007-11-19 BR BRPI0718639-8A patent/BRPI0718639A2/en not_active Application Discontinuation
- 2007-11-19 CN CN2007800427077A patent/CN101541343B/en not_active Expired - Fee Related
- 2007-11-19 RU RU2009123478/10A patent/RU2462263C2/en not_active IP Right Cessation
- 2007-11-19 UA UAA200904648A patent/UA95652C2/en unknown
- 2007-11-19 ES ES07822693T patent/ES2380134T3/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107789622A (en) * | 2017-10-18 | 2018-03-13 | 山东农业大学 | A kind of calf enterotoxemia C.perfringens β2The preparation method of toxin toxoid vaccine |
Also Published As
| Publication number | Publication date |
|---|---|
| UA95652C2 (en) | 2011-08-25 |
| RU2009123478A (en) | 2010-12-27 |
| TWI369991B (en) | 2012-08-11 |
| CN101541343B (en) | 2012-05-16 |
| ES2380134T3 (en) | 2012-05-08 |
| RU2462263C2 (en) | 2012-09-27 |
| ATE540692T1 (en) | 2012-01-15 |
| TW200831121A (en) | 2008-08-01 |
| BRPI0718639A2 (en) | 2013-11-26 |
| DK2086578T3 (en) | 2012-05-14 |
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Granted publication date: 20120516 Termination date: 20201119 |