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 piglets having maternally derived anti-Streptococcus suis antibodies against Streptococcus suis, by administering the vaccine to the piglets at an age of at most 28 days, preferably before the piglets are weaned.

Claims

1. A method for protecting piglets having maternally derived anti-Streptococcus suis antibodies against Streptococcus suis, comprising administering a vaccine comprising an IgM protease antigen of Streptococcus suis to the piglets at an age of at most 28 days.

2. The method of claim 1, comprising administering one shot of the vaccine.

3. The method of claim 1, wherein the administering of the vaccine is before an age at which the piglets are weaned.

4. The method of claim 1, wherein the method is for conferring protection against clinical signs associated with a pathogenic infection with Streptococcus suis.

5. The method of claim 1, wherein the method is for conferring protection against an increased mortality associated with a pathogenic infection with Streptococcus suis.

6. The method of claim 1, wherein the IgM protease antigen is present in an amount below 250 μg per dose of the vaccine, preferably below 120 μg per dose.

Description

EXAMPLES

Example 1

(1) As protection against Streptococcus suis for piglets is required 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 antiSsuis positive piglets at an age of 3 weeks. The aim of the present study was to test whether the vaccine is efficacious as a one-shot vaccine (in two different formulations) in comparison to a regular bacterin vaccine.

(2) Study Design

(3) Thirty 3-week-old anti-Ssuis MDA positive piglets were used for the experiment. The piglets were allotted to three groups (evenly distributed over the different litters) of 10 piglets each. Group 1 was vaccinated once intramuscularly at 3 weeks of age with a recombinant rldeSsuis IgM protease antigen (Seele et al: Vaccine 33:2207-2212; 5 May 2015, par. 2.2.) at 250 μg per dose (as established by a Bradford protein assay using BSA as a standard) in the commercially available Emulsigen adjuvant (Phibro Animal Health, Teaneck, USA). Group 2 was vaccinated once intramuscularly (2 ml) at 3 weeks of age with the recombinant rldeSsuis IgM protease (250 μg per dose; Bradford protein assay using bovine serum albumin as a standard) in the commercially available X-Solve adjuvant (MSD Animal Health, Boxmeer, The Netherlands). Group 3 was vaccinated once intramuscularly at 3 weeks of age with a bacterin vaccine (2×10.sup.9 cells) in X-Solve, using inactivated Streptococcus suis serotype 2 bacteria, comparable to the antigen as present in the commercially available vaccine Porcilis Strepsuis (MSD Animal Health). 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 Ssuis serotype 2. After challenge the pigs were daily observed for clinical signs associated with a pathogenic Ssuis infection such as depression, locomotory problems, increased respiration rate and neurological signs using a regular scoring system going from 0 (no signs) to 3 for severe cases. The same scoring system (0 for parameter not visible, the highest number for severe cases) was used for the other parameters. Just before vaccination and challenge serum blood was collected for antibody determination using an experimental Ssuis antibody ELISA against whole cells. At regular times before and after challenge heparin blood was collected for re-isolation of challenge strain. 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.

(6) TABLE-US-00001 TABLE 1 Post challenge data Survival time Peak temp Blood reisolation Group (d) (° C.) Clinical score score 1 5.4 40.6 27.2 1.9 2 5.9 40.5 17.8 1.4 3 3.2 41.2 59.2 4.7

(7) The post-mortem scores for the joints (score going from 0 to 3 if fibrinous material is present), joint reisolation (score going from 0 to 4 when the amount of CFU is over 1000), the internal organs (score going from 0 to 3 for lungs and abdominal cavity/pleura and pericard and from 0 to 4 for Meninges) and organ reisolation (score going from 0 to 4 when the amount of CFU is over 1000) are given in table 2.

(8) TABLE-US-00002 TABLE 2 Average post mortem scores Joint Internal Organ Group Joint reisolation organs reisolation 1 0.8 6.1 2.0 7.1 2 0.4 3.4 1.4 4.4 3 5.3 17.4 4.2 13.9

(9) Conclusion

(10) All parameters were improved in the two IgM protease vaccine groups 1 (Emulsigen adjuvant) and 2 (X-Solve adjuvant) when compared to the bacterin group 3. The vaccine formulated in XSolve appeared to induce better protection than the vaccine as used in Group 1: all 8 parameters tested were significantly improved in group 2 as compared to group 3, and 3 of 8 parameters (viz. “survival time”, “joint reisolation score” and “internal organs score”) were significantly improved in group 1 as compared to group 3. In conclusion, the results demonstrate that a one-shot IgM protease subunit vaccine at 250 μg/dose induced protection in 3-week-old MDA positive piglets against a pathogenic infection with Streptococcus suis serotype 2, when challenged 3 weeks after vaccination, 2 weeks after weaning and immediately after transport.

Example 2

(11) A second experiment was run which was basically the same as the first experiment (see here above under Example 1), using MDA positive piglets at an early age, before weaning, but wherein a lower dose of the IgM protease was used (120 μg per dose in each case), and wherein in a first group (Group1) an alternative Xsolve adjuvant was used (having the same constituents as the Xsolve adjuvant in Example 1 but only at 60% of the concentration thus being milder). Group 2 received the antigen formulated in the alum based adjuvant Emunade (MSD Animal Health, Boxmeer, The Netherlands). Group 3 served as a negative challenge control group. No positive control group was used in this experiment

(12) Other differences between the two experiments are that in this experiment the piglets are slightly older at day of vaccination (3% weeks) and 1 week older (7 weeks) at day of challenge.

(13) The vaccines appeared to be safe after administration. The results of the challenge experiment are indicated here beneath.

(14) TABLE-US-00003 TABLE 3 Post challenge data Early euthanisations Peak temp Clinical Blood Group (#) (° C.) score reis. score 1 2/10 40.4 16.4 0.5 2 3/10 40.6 13.2 1.1 3 8/10 40.9 52.0 2.7

(15) The results during the clinical phase indicate that all parameters are improved for each vaccine. The post-mortem data are indicated in Table 4. Also from the post-mortem data it appears that the vaccines, although at a lower dose and using milder adjuvants than the adjuvant used in the first experiment, are able to protect against Streptococcus suis. Based on these data it is believed that protection against Streptococcus suis can also be obtained when using a dosis below 120 μg, in particular a dosis between 1 and 120 μg according to a specific embodiment of the vaccine for use according to the invention as outlined here above.

(16) TABLE-US-00004 TABLE 4 Average post mortem scores Joint Internal Organ Group Joint reisolation organs reisolation 1 0.4 0.3 0.4 0.6 2 0.8 1.3 0.3 1.6 3 2.1 1.5 1.7 3.9