Vaccine for protection against <i>Streptococcus suis</i>

Abstract

The present invention pertains to a vaccine comprising an IgM protease antigen of Streptococcus suis, for use in a method for protecting pigs against an infection with Streptococcus suis of serotype 2 and against an infection with Streptococcus suis of serotype 14.

Claims

1. A method for protecting a pig against both a pathogenic infection with Streptococcus suis of serotype 2 and a pathogenic infection with Streptococcus suis of serotype 14, comprising administering a vaccine comprising an IgM protease antigen of Streptococcus suis to the pig; wherein the pig has maternally derived anti-Streptococcus suis antibodies.

2. The method for protecting the pig of claim 1, comprising administering the antigen only once to the pig.

3. The method for protecting the pig of claim 1, comprising administering the antigen to the pig at an age of at most 28 days.

4. The method for protecting the pig of claim 1, comprising administering the antigen before an age at which the pig is weaned.

5. The method for protecting the pig of claim 1, wherein the method confers protection against mortality associated with a pathogenic infection with Streptococcus suis of serotype 2 and serotype 14.

Description

EXAMPLES

Example 1

(1) The aim of the first study was to test whether an IgM protease antigen, in this case IgM protease antigen of Streptococcus suis serotype 2, is able to provide protection against a challenge with Streptococcus suis of serotype 2 in comparison to a regular bacterin vaccine containing killed serotype 2 S. suis bacteria (cf. Porcilis Strepsuis).

(2) Study Design

(3) Thirty weaned pigs were used. The pigs were allotted to three groups (evenly distributed over the different litters) of 10 pigs each. Group 1 was vaccinated twice intramuscularly at 5 and 7 weeks of age with a recombinant rIdeSsuis IgM protease antigen (Seele et al: Vaccine 33:2207-2212; 5 May 2015, par. 2.2.) at 230 μg per dose (as established by a Bradford protein assay using BSA as a standard) in oil-in-water adjuvant. Group 2 was vaccinated twice intramuscularly at 5 and 7 weeks of age with a serotype 2 whole cell bacterin (cf Porcilis Strepsuis) in oil-in-water adjuvant (positive control). Group 3 was left unvaccinated and served as challenge control. At 9 weeks of age the pigs were challenged with a virulent culture of S. suis serotype 2. At regular times before and after challenge heparin blood was collected for re-isolation of challenge strain. After challenge the pigs were observed daily for clinical signs of S. suis infection (such as depression, locomotory problems and/or neurological signs) and scored using a regular scoring system going from 0 (no signs) to 3 for severe cases. Severely affected animals were euthanized and post-mortem examined. At the end of the study (7 days after challenge) all surviving pigs were euthanized and post-mortem examined.

(4) Results

(5) None of the vaccines induced any unacceptable site or systemic reactions and thus could be considered safe. The post challenge data for the period before euthanisation (at day 7) are indicated in Table 1. It is noted that on the day of challenge one pig in Group 1 appeared to be a runt and it was decided not to challenge this animal. The average clinical scores, the number of dead animals after challenge and the number of animals from which the pathogen could be re-isolated from the blood appeared to be improved for both vaccines.

(6) TABLE-US-00001 TABLE 1 Post challenge data Study 1 Average Dead Positive clinical after blood Group score challenge isolation 1 11 1/9 2/9 2 33  5/10  6/10 3 61 10/10 10/10
Conclusion

(7) As expected, the inactivated whole cell vaccine induced significant homologous protection. The IgM protease antigen induced even better protection against an infection with Streptococcus suis serotype 2.

Example 2

(8) The aim of the second study was to test whether the IgM protease antigen is able to provide protection against a challenge with Streptococcus suis of serotype 14.

(9) Study Design

(10) The design of the study was in essence the same as of the first study. Groups of 10 pigs were used and vaccinated twice at the age of 5 and 7 weeks with the IgM protease antigen (Group 1) or they were left as unvaccinated control animals (Group 2). At 9 weeks of age the pigs were challenged with a virulent culture of S. suis serotype 14.

(11) Results

(12) Also in this study the vaccine did not induce any unacceptable site or systemic reactions. On day of first vaccination (5 weeks of age) most pigs had a (maternally derived) antibody titre of about 4 log 2. After vaccination, the vaccine group showed good antibody responses with average antibody titres of 9.3 log 2 after booster vaccination. The antibody titres of the control animals remained at a low level with average antibody titres of 4.1 log 2. The post challenge data for the period before euthanisation (at day 11 after challenge) are indicated in Table 2 (ACS=average clinical score; APT=average peak temparture; AST=average survival time; DAC=Dead after challenge; PBI=positive blood isolation)

(13) TABLE-US-00002 TABLE 2 Post challenge data Study 2 Group ACS APT AST DAC PBI 1 1.3 40.0 11.0 0/10 0/10 2 16.9 40.5 9.4 2/10 2/10
Conclusion

(14) Although in this study the challenge appeared to be less virulent, the results demonstrate that the IgM protease antigen induces protection against S. suis serotype 14 challenge. This was demonstrated by a reduction in clinical scores, the number of animals reaching the humane endpoint, and the number of animals from which the challenge bacterium could be reisolated from the blood. Next to this it appeared that the average survival time for the vaccinated animals was better. Together with the data of the first study, the conclusion can be drawn that the IgM protease antigen is able to provide protection against a pathogenic Streptococcus suis infection with bacteria of serotype 2 and serotype 14. This means, also taking into account the high identity between IgM protease of serotype 2 and IgM protease of serotype 14, that cross-protection between these serotypes has been demonstrated (i.e. IgM protease of Streptococcus suis serotype 2 protects against serotype 14 challenge and vice versa). Also, it appears that the level of protection against both serotypes corresponds to (or is even better) than the level of homologous protection obtainable with a commonly available serotype 2 bacterin vaccine.

Example 3

(15) As protection against Streptococcus suis for pigs is preferably obtained in the risk period (typically 4-7 weeks of age) it was assessed whether an IgM protease containing vaccine is efficacious as a one shot vaccine in maternally derived anti-Streptococcus suis positive pigs at an age of 3 weeks.

(16) Study Design

(17) The study design was comparable to that of the first two studies, with the main difference that instead of 5 week old animals, 3 week old anti-Ssuis MDA positive piglets were vaccinated (only 1 out of 10 animals appeared to have an MDA level below detection limit). Group 1 was vaccinated once intramuscularly with the IgM protease antigen in an oil-in-water adjuvant. Group 2 served as a negative challenge control group. At 4 weeks of age the piglets were weaned. At 6 weeks of age the piglets were transported to the challenge room and challenged immediately. There was no acclimatization period between the transport and the challenge to mimic natural stress. The piglets were challenged with a virulent culture of Streptococcus suis serotype 2.

(18) Results

(19) The vaccines did not induce any unacceptable site or systemic reactions. The post challenge data for the period before euthanisation (at day 7) are indicated in Table 3. On the day of challenge one pig in Group 2 appeared to be a runt and it was decided not to challenge this animal.

(20) TABLE-US-00003 TABLE 3 Post challenge data Study 3 Average Dead Positive clinical after blood Group score challenge isolation 1 18  3/10  3/10 2 43 7/9 7/9
Conclusion

(21) In conclusion, the results demonstrate that by administering the IgM protease antigen only once adequate protection can be induced in 3 week old MDA positive piglets against a pathogenic infection with Streptococcus suis, even when challenged 3 weeks after vaccination, 2 weeks after weaning and immediately after transport. Although this has been demonstrated with a serotype 2 challenge only, since example 2 shows that the antigen is capable of inducing protection against serotype 14 as well, it is understood that comparable results are obtained when aiming at protection against a serotype 14 infection in this type of pigs.