RU2802072C2 - Vaccine for protection against streptococcus suis - Google Patents

Abstract

FIELD: biotechnology; veterinary medicine.

SUBSTANCE: following is proposed: the use of IgM protease antigen of serotype 2 Streptococcus suis in a method of protecting pigs against a pathogenic infection of serotype 2 Streptococcus suis and against a pathogenic infection of serotype 14 Streptococcus suis, as well as a method of protecting pigs against a serotype 2 Streptococcus suis infection and against a serotype 14 Streptococcus suis infection.

EFFECT: invention allows to protect pigs simultaneously against pathogenic infection of serotype 2 Streptococcus suis and against pathogenic infection of serotype 14 Streptococcus suis.

9 cl, 3 tbl, 3 ex

Description

FIELD OF THE INVENTION

The invention relates to the protection of pigs from pathogenic infection with Streptococcus suis bacteria of various serotypes.

BACKGROUND OF THE INVENTION

Streptococcus suis ( S. suis ) is one of the main etiological factors of a contagious bacterial disease in pigs. This pathogen can cause a variety of clinical syndromes including meningitis, arthritis, pericarditis, polyserositis, septicemia, pneumonia, and sudden death. S. suis is a gram-positive facultative anaerobic coccus, originally defined as belonging to the Lancefield groups R, S, R/S, or T. More recently, a new typing system has been proposed based on type-specific capsular polysaccharide antigens found on the cell wall. This resulted in a system containing 35 serotypes (Rasmussen and Andresen, 1998, "16S rDNA sequence variations of some Streptococcus suis serotypes", Int. J. Syst. Bacteriol. 48, 1063-1065), of which serotypes 2, 9, 1 , 7 and 1/2 are the most common, while serotype 14 is particularly common in Europe. The control of Streptococcus suis in swine herds has proven to be very difficult. Streptococcus suis is a commensal and opportunistic pathogen of pigs. Obviously, the immune system is not triggered in every case of infection. Further, Streptococcus suis is a highly encapsulated pathogen and uses an arsenal of virulence factors to elude the host's immune system. Taken together, these characteristics have made it difficult to develop effective vaccines to control this important pathogen. A review article has recently been published regarding vaccines against Streptococcus suis (Mariela Segura: " Streptococcus suis vaccines: candidate antigens and progress, Expert Review of Vaccines , Volume 14, 2015, Issue 12, pages 1587-1608). In this review, the clinical field information and experimental data to review the state of the art in Streptoccus suis vaccine development as described herein below.

Vaccines currently in use are mostly whole cell bacterins. However, site reports describe the difficulty of monitoring and managing the course of the disease and, in particular, "vaccine failure" is common. Pigs are the main source of infection, and both vertical and horizontal transmission are involved in the spread of the disease in the herd. Combining carrier animals with susceptible animals under conditions of stress such as weaning and transport usually results in clinical disease. Medicinal early withdrawal practices and isolated early withdrawal practices do not eliminate Streptococcus suis infection. Thus, effective control measures to prevent disease depend on prophylactic/metaphylactic procedures (when appropriate) and on vaccination. Currently, local immunization efforts are focused on the use of commercial or autogenous bacterins. These vaccine strategies are used for either piglets or sows. From weaning onwards, piglets are more prone to Streptococcus suis infections due to the stresses associated with weaning as well as frequent subsequent transport. Thus, antenatal immunization is often used in an attempt to create and confer passive immunity in piglets and provide protection against Streptococcus suis in these stressful conditions early in life. Moreover, vaccination of sows is less expensive and labor intensive, thus representing an economic alternative to vaccination of piglets. However, the available results seem to indicate that vaccination of sows with bacterins is also controversial. In many cases, vaccinated sows, even if they are vaccinated twice before parturition, respond poorly or not at all to vaccination, resulting in low maternal immunity passed on to offspring. And even if maternal immunity is transmitted at a sufficient level, in many cases the levels of maternal antibodies are too low to provide protection during the most critical period at 4-7 weeks of age.

Autogenous bacterins are often used locally in piglets, especially in Europe. They are obtained from a virulent strain isolated from a farm with clinical problems and used on the same farm. One disadvantage of autogenous bacterins is that vaccine safety data are lacking and severe adverse reactions can occur. Sampling errors (due to the use of only one or two pigs or samples) may result in the inability to identify the strain or serotype associated with the last outbreak. This impossibility can be especially problematic in endemic herds. Finally, the most important dilemma of autogenous bacterins is that their actual efficacy is poorly researched. Since the use of autogenous vaccines is empirical, it is not surprising that the results obtained for these vaccines are inconsistent.

Other experimental vaccines are also described in the art. Kai-Jen Hsueh et al. showed ("Immunization with Streptococcus suis bacterin plus recombinant Sao protein in sows conveys passive immunity to their piglets": BMC Veterinary Research, BMC series - open, inclusive and trusted, 13:15, 7 January 2017) that the bacterin plus subunit can be the basis for successful vaccination of sows to impart protective immunity to their piglets.

Live attenuated vaccines are also described in the art. Non-encapsulated isogenic mutants of Streptococcus suis serotype 2 were shown to be avirulent. However, a live vaccine formulation based on a non-encapsulated serotype 2 mutant induced only partial protection against death and did not prevent the development of clinical signs in pigs infected with the wild-type strain (Wisselink HJ, Stockhofe-Zurwieden N, Hilgers LA, et al. "Assessment of protective efficacy of live and killed vaccines based on a non-encapsulated mutant of Streptococcus suis serotype 2": Vet Microbiol . 2002, 84:155-168).

An extensive list of Streptococcus suis immunogenic molecules has been described over the past few years, and most of these have been discovered through immunoproteomics using either sera from recovered infected pigs or humans and/or laboratory-derived immune sera. WO2015/181356 (IDT Biologika GmbH) shows that IgM protease antigens (either the whole protein or a highly conserved Mac-1 domain corresponding to only approximately 35% of the total protein) can induce a protective immune response in piglets in a vaccination schedule consisting of administering two doses of IgM protease antigen, optionally in combination with a primer vaccination containing bacterin. It is noted that WO2017/005913 (Intervacc AB) also describes the use of an IgM protease antigen (in particular, an IgM protease polypeptide fused to a nucleotidase). However, only the property of being able to induce a serological response has been shown. This international patent application does not show the protective effect of the IgM protease antigen.

Another factor that exacerbates the problem of providing adequate protection against Streptococcus suis is the lack of heterologous protection in existing vaccines. For example, Porcilis Strepsuis® is a registered vaccine (available from MSD Animal Health and Coopers Animal Health) to protect pigs against Streptococcus suis serotype 2. It also passively protects offspring from serotype 2 through colostrum ingestion. Also, as is known from WO 2010/108977, when the vaccine is administered to sows, the offspring appear to have some (very low) level of protection against heterologous challenge. However, such passive protection is very short-lived. In addition, this vaccine has never been registered to protect offspring by ingestion of colostrum against Streptococcus suis of any other serotype, so it appears that the level of heterologous protection was too low to meet registration standards. This is consistent with commonly known information that for vaccines against Streptococcus suis , protection against bacteria of serotypes not included in the vaccine does not occur. This is confirmed, inter alia, in the doctoral dissertation of Hendrikus Jan Wisselink entitled "Streptococcus suis infection in pigs: Use of virulence-associated markers in diagnostics and vaccines", published on December 6, 2001. The summary (p. 129) states that "The strategy for preventing S. suis disease is the use of vaccines. Killed whole cell vaccines appear to induce significant protection against challenge with strains of the homologous serotype, but this protection is likely to be serotype -specific".

There is data consistent with those of Smith (US 7125548; published October 24, 2006). She states that "antibodies are serotype-specific, and often confer protection against only one of the many serotypes known within the Streptococci group. fractions of S. suis provide only limited protection against heterologous strains" (column 4, lines 42-28 of the US patent). A study published in January 2008 (Medycyna Weterynaryjna, Volume 64, issue 1, pages 113-116) described protection against S. suis serotypes 2 and 1/2. If there were any expected level of heteological protection between different serotypes, it would exist between these serotypes, since they are immunologically very closely related. However, both serotypes were included in the vaccine to provide adequate protection. The UK-based RUMA (Responsible Use of Medicines in agriculture Alliance) published guidance on the use of vaccines and vaccination in pig production in November 2006. With regard to disease caused by S. suis , this guideline states (on page 19) that protection in the pig can be achieved by vaccination of the sow, but that "protection against disease caused by other serotypes of Strep. suis is unlikely to occur".

OBJECT OF THE INVENTION

The aim of the invention is to find a vaccine that is effective in protecting pigs against Streptococcus , in particular against the two common serotypes 2 and 14. based on bacteria.

SUMMARY OF THE INVENTION

To accomplish the main object of the invention, it has been found that the IgM protease antigen of Streptococcus suis can be used in a method of protecting pigs against pathogenic infection of Streptococcus suis serotype 2 and against pathogenic infection of Streptococcus suis serotype 14. The IgM protease antigen is usually found in the vaccine composition, i.e. e. a composition safe for administration to pigs wherein the antigen is admixed with a pharmaceutically acceptable carrier for ease of administration. By administering the antigen to pigs, the pigs were found to be protected against pathogenic infection by the bacteria Streptococcus suis serotype 2 and serotype 9. In addition, the level of protection against both serotypes was found to correspond to the level of homologous protection achieved with the conventional bacterin-based vaccine against the serotype 2 ( c.f. Porcilis Strepsuis). This means that heterologous protection has been shown for an IgM protease antigen between at least serotype 2 and serotype 14. This is the first time that sufficient active protection has been shown against Streptococus suis bacteria of at least serotype 2 and serotype 14 using only one antigen, in particular the first time it was shown using an IgM protease antigen. This provides a unique opportunity to vaccinate the pigs themselves and induce active heterologous protection instead of using short-term passive protection, which can be achieved through colostrum of immunized mother animals, as known from WO2010/108977. Further, the true level of protection, both homologous and heterologous, appears to be significantly better than is achieved using the known bacterin-type vaccine.

The invention also relates to the use of an IgM protease antigen of Streptococcus suis for obtaining a vaccine for protecting pigs against a pathogenic infection of Streptococcus suis serotype 2 and against a pathogenic infection of Streptococcus suis serotype 14, and to a method for protecting pigs from a pathogenic infection of Streptococcus suis serotype 2 and against a pathogenic infection of Streptococcus suis serotype 14 by administering a vaccine containing the Streptococcus suis IgM protease antigen to pigs.

As noted above, in a vaccine, the antigen is typically combined with a pharmaceutically acceptable carrier, ie. biocompatible environment, i.e. a medium which, upon administration, does not induce significant adverse reactions in the animal in question, and which is capable of presenting the antigen to the host animal's immune system upon administration of the vaccine. Such a pharmaceutically acceptable carrier may be, for example, a liquid containing water and/or any other biocompatible solvent or solid carrier, such as the carrier often used to prepare lyophilized vaccines (based on sugars and/or proteins), optionally containing immunostimulatory substances (adjuvants). ). Optionally, other substances are added, such as stabilizers, viscosity modifiers, or other components, depending on the intended use and desired properties of the vaccine.

DEFINITIONS

Streptococcus suis IgM protease antigen is an enzyme that specifically degrades porcine IgM (but not porcine IgG or porcine IgA; Seele at al, in Journal of Bacteriology , 2013, 195 930-940; and Vaccine 33:2207-2212; 5 May 2015), a protein referred to as IdeSsuis, or an immunogenic portion thereof (generally having a length of at least about 30-35% of the full length enzyme). The whole enzyme has a mass of approximately 100-125 kDa, corresponding to approximately 1000-1150 amino acids, the size depending on the S. suis serotype. WO 2015/181356 provides several sequences that correspond to the IgM protease antigen of Streptococcus suis , namely, SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:5, the latter being the immunogenic portion of the full length enzyme (referred to as the Mac-1 domain, ie amino acids 80-414 of SED ID NO:7). Other examples of immunogenic portions of a full length enzyme are given in WO2017/005913. In particular, the IgM protease may be a protease according to SEQ ID NO:1 WO2015/1818356 or a protein having at least 90%, or even 91, 92, 93, 94, 95, 96, 97, 98, 99%, up to up to 100% sequence identity in overlapping regions. Amino acid sequence identity can be established by the BLAST program using the blastp algorithm with default parameters. Streptococcus suis IgM proteases of different serotypes are expected to have sequence identity greater than 90%, in particular, it is expected to be 91, 92, 93, 94, 95, 96, 97, 98, 99% and up to 100%. An artificial protein, for example, can be made to optimize the yield of a recombinant production system for an antigen, can have a lower amino acid sequence identity such as 85%, 80%, 75%, 70%, or even 60% compared to the whole enzyme, while maintaining the desired immunogenic function, and within the scope of the present invention, it is understood as an IgM protease antigen of Streptococcus suis .

Protection against a pathogenic infection by a microorganism is the same as achieving protective immunity, i.e. contributing to the prevention, mitigation, or cure of a pathogenic infection by that microorganism, or a disorder resulting from that infection, such as preventing or reducing an actual infection or one or more clinical signs of a pathogenic infection by that pathogen.

A method involving administration of the antigen only once means that protective immunity is conferred after only one injection of the antigen and thus there is no booster vaccination to achieve said protective immunity. It is understood that in a two-shot regimen, the first (primer) vaccination is usually followed by a booster within 6 weeks of the first shot, usually within 3 or even 2 weeks of the first shot, and only after the second (booster) shot is protective immunity achieved, i.e. .e. successful defense as defined herein above.

EMBODIMENTS FOR CARRYING OUT THE INVENTION

In a first embodiment of the present invention, the method comprises administering the antigen to pigs only once. Surprisingly, only one injection of antigen was able to induce protective immunity in pigs. In the art, non-live Streptococcus suis vaccines have always been administered in a priming-assisted administration regimen, and yet they have had poor efficacy. As for the antigen for use in the present invention, in the art (see WO2015/181356 and WO2017/005913) this antigen has invariably been used in a two injection approach, optionally using a multicomponent vaccine (i.e. containing more than just the protease antigen IgM). Thus, it was surprisingly found that a single dose with IgM protease was able to induce immunity in pigs.

In a second embodiment, the method comprises administering the antigen to pigs less than 28 days old. As described herein above, Streptococcus suis is a commensal and opportunistic pathogen of pigs. In particular, under stress conditions, this bacterium can induce pathogenic infection and induce disease. In current swine production conditions, the main stress is induced at or after the pigs are 28 days old, for example induced by weaning piglets (3-4 weeks) and transporting young piglets shortly thereafter. To protect against pathogenic Streptococcus suis infection, pigs must therefore receive their vaccine at a very young age, typically before reaching 28 days of age. It was found that using the IgM protease antigen in pigs aged no more than 28 days, i. any age from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28 days, sufficient (heterologous) protection can be achieved. As is known in the art, in particular from WO2017/005913, a positive immune response against an IgM protease antigen can be achieved in young pigs from birth onwards. This means, given the demonstration to date of actual protection in pigs at 25 days of age, it is clear that protection can be achieved even at a younger age.

In another embodiment, the method comprises administering the antigen prior to weaning age of the piglets. In other words, the antigen is administered before the age at which piglets are usually weaned (typically at 3-4 weeks of age). It has been shown that by using the antigen at this early stage, heterologous protection against stress-induced pathogenic Streptococcus suis infection can be achieved within a short window of 2-3 weeks immediately after weaning. It is known that WO2015/181356 presents successful vaccination using IgM protease as antigen. However, apart from the fact that heterologous protection is not indicated, the vaccine was used in piglets at 5-7 weeks of age and challenged at 9 weeks of age, thus well after the period of risk (i.e. the period of maximum occurrence of pathogenic Streptococcus suis infections). ) 2-3 weeks after weaning/transport, i.e. at the age of 5-7 weeks. Thus, without any evidence of efficacy under practical conditions (i.e. infection within a window of 2-3 weeks after withdrawal and transport stress), it is still unclear, beyond the question of whether heterologous protection can be achieved, whether IgM protease/bacterin combination vaccine strategy as described in WO 2015/181356 under practical conditions.

In yet another embodiment, the method comprises administering the antigen to pigs having antibodies against maternally derived Streptococcus suis . Active vaccination of young animals has the risk of possibly being interfered with by maternal antibodies produced either by natural infection or by active immunization of sows (Baums CG, Bruggemann C, Kock C, et al. "Immunogenicity of an autogenous Streptococcus suis bacterin in preparturient sows and their piglets in relation to protection after weaning": Clin Vaccine Immunol . 2010;17:1589-1597). Indeed, neither vaccination of breastfed piglets nor vaccination of piglets weaned from immunized sows was associated with a pronounced active immune response and protection at 8 weeks of age. This failure was associated with a strong inhibitory effect of maternal antibodies or other colostrum components. In this regard, it was also possible to demonstrate an interference between maternal antibodies and active production of antibodies against S. suis in a field study after vaccination with an autologous vaccine formulation of the capsule type against S. suis 1/2 (Lapointe L, D'Allaire S, Lebrun A, et al.: "Antibody response to an autogenous vaccine and serologic profile for Streptococcus suis capsular type 1/2.": Can J Vet Res . 2002; 66:8-14). A field study aimed at determining the efficacy of a single dose protocol of S. suis serotype 14 bacterin in fed piglets at 4 days of age also showed no protection of piglets against homologous challenge (Amass SF, Stevenson GW, Knox KE, et al. "Efficacy of an autogenous vaccine for preventing streptococcosis in piglets": Vet Med . 1999, 94, 480-484). Thus, it was surprising that using an IgM protease antigen sufficient protection could be achieved in the presence of antibodies against maternally derived Streptococcus suis antigens.

In another embodiment, the method is designed to provide protection against mortality associated with pathogenic Streptococcus suis serotype 2 and serotype 14 infection.

In another embodiment, the method is designed to provide protection against clinical signs associated with pathogenic Streptococcus suis serotype 2 and serotype 14 infection. increased respiratory rate and neurological signs (eg, tremor, convulsions, torticollis, ataxia). Prevention, mitigation or cure of one or more of these traits would be beneficial to pigs, in addition to suppressing pathogenic infection.

The invention is further explained on the basis of the following examples.

EXAMPLES

EXAMPLE 1

The aim of the first trial was to test whether an IgM protease antigen, in this case an IgM protease antigen of Streptococcus suis serotype 2, is capable of conferring protection against infection with Streptococcus suis serotype 2 compared to a standard bacterin-based vaccine containing killed S. suis serotype 2 bacteria ( cf. Porcilis Strepsuis).

Study scheme

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

results

None of the vaccines induced any unacceptable injection site or systemic reactions and thus could be considered safe. Post-challenge data for the pre-kill period (Day 7) are shown in Table 1. It should be noted that on the day of challenge, one pig in group 1 was undersized and it was decided not to challenge this animal. The mean clinical scores, the number of dead animals, and the number of animals from whose blood the pathogen could be reisolated were found to be the best for both vaccines.

Table 1 : Post-infection data for study 1

Group Mean clinical score Died after being infected positive blood excretion 1 eleven 1/9 2/9 2 33 5/10 6/10 3 61 10/10 10/10

Conclusion

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

EXAMPLE 2

The aim of the second study was to test whether the IgM protease antigen is capable of conferring protection against challenge with Streptococcus suis serotype 14.

Study scheme

The design of the study was essentially the same as for the first study. Groups of 10 were used and they were vaccinated twice at 5 and 7 weeks of age with IgM protease antigen (Group 1) or left as unvaccinated controls (Group 2). At 9 weeks of age, pigs were challenged with a virulent cultureS. suisserotype 14.

results

Also in this study, the vaccine did not induce any unacceptable injection site or systemic reactions. On the day of the first vaccination (5 weeks of age), most pigs had an antibody titer (maternal origin) of approximately 4 log 2. Post-vaccination, the vaccine group showed good antibody responses with mean antibody titers of 9.3 log 2 after booster vaccination. Antibody titers in control animals remained low with mean antibody titers of 4.1 log2. Post-challenge data for the period before sacrifice (day 11 post-challenge) are shown in Table 2 (ACS=mean clinical score; APT=mean peak temperature; AST=mean survival time; DAC=death after challenge; PBI=positive blood isolation)

table 2 : Post-infection data for trial 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

Although the challenge appears to be less virulent in the study, the results demonstrate that the IgM protease antigen induces protection against S. suis serotype 14 challenge. from whose blood the infecting bacterium could be re-isolated. Further, it turned out that the average survival time for vaccinated animals was the best. Together with the data from the first study, it can be concluded that the IgM protease antigen is capable of conferring protection against pathogenic Streptococcus suis infection by serotype 2 and serotype 14 bacteria. cross-protection between these serotypes (i.e. IgM protease of Streptococcus suis serotype 2 protects against infection with serotype 14 and vice versa). It also appeared that the level of protection against both serotypes was equal to (or even better than) the level of homologous protection achieved using a commonly available vaccine based on bacterin serotype 2.

EXAMPLE 3

Because protection against Streptococcus suis is preferably achieved in pigs at risk (typically 4-7 weeks of age), an assessment was made as to whether the vaccine containing IgM protease is effective as a single dose vaccine in piglets positive for maternal Streptococcus suis antibodies. origin, at the age of 3 weeks.

Study scheme

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

results

The vaccines did not induce any unacceptable administration site or systemic reactions. Post-infection data for the period prior to sacrifice (day 7) are shown in Table 3. On the day of infection, one pig in group 2 was undersized and it was decided not to infect this animal.

Table 3 : Post-infection data for study 3

Group Mean clinical score Died after being infected positive blood excretion 1 18 3/10 3/10 2 43 7/9 7/9

Conclusion

In conclusion, the results demonstrate that by administering the IgM protease antigen only once, sufficient protection can be induced in MDA-positive 3-week-old piglets against pathogenic Streptococcus suis infection, even when challenged 3 weeks post-vaccination, 2 weeks post-vaccination. withdrawal and immediately after transportation. Although this has only been demonstrated for serotype 2 infection, since example 2 shows that the antigen is able to induce protection against serotype 14 as well, it is understood that comparable results will be obtained when protection against serotype 14 infection is the goal in this type of piglet.

Claims (9)

1. Use of IgM protease antigen of Streptococcus suis serotype 2 in a method for protecting pigs against pathogenic infection of Streptococcus suis serotype 2 and against pathogenic infection of Streptococcus suis serotype 14. 2. Use according to claim 1, characterized in that the method comprises administering the antigen to pigs only once. 3. Application according to any one of paragraphs. 1 or 2, characterized in that the method includes the introduction of the antigen to pigs aged no more than 28 days. 4. Application according to any one of paragraphs. 1-3, characterized in that the method includes the introduction of antigen before the age of weaning piglets. 5. Application according to any one of paragraphs. 1-4, characterized in that the method includes the introduction of the antigen to pigs having antibodies against Streptococcus suis of maternal origin. 6. Application according to any one of paragraphs. 1-5, characterized in that the method is designed to provide protection against mortality associated with pathogenic infection with Streptococcus suis serotype 2 and serotype 14. 7. Application according to any one of paragraphs. 1-6, characterized in that the method is designed to provide protection against clinical signs associated with pathogenic infection with Streptococcus suis serotype 2 and serotype 14. 8. Use of the IgM protease antigen of Streptococcus suis serotype 2 to obtain a vaccine to protect pigs against pathogenic infection of Streptococcus suis serotype 2 and against pathogenic infection of Streptococcus suis serotype 14. 9. A method for protecting pigs against a pathogenic infection of Streptococcus suis serotype 2 and against a pathogenic infection of Streptococcus suis serotype 14 by administering to pigs a vaccine containing an IgM protease antigen of Streptococcus suis serotype 2.