Antibody Response Specific to the Capsular Polysaccharide Is Impaired in Streptococcus suis Serotype 2-Infected Animals

Abstract

bStreptococcus suis serotype 2 is an extracellular encapsulated bacterium that causes severe septicemia and meningitis in swine and humans. Albeit crucial in the fight against encapsulated bacteria, the nature of the capsular polysaccharide (CPS)-specific antibody (Ab) response during S. suis type 2 infection is unknown. We compared for the first time the features of CPS-specific versus protein-specific Ab responses during experimental infections with live virulent S. suis type 2 in mice. The primary protein-specific Ab response was dominated by both type 1 and 2 IgG subclasses, whereas IgM titers were more modest. The secondary protein-specific Ab response showed all of the features of a memory response with faster kinetics and boosted the titers of all Ig isotypes. In contrast, the primary CPS-specific Ab response was either inexistent or had titers only slightly higher than those in noninfected animals and was essentially composed of IgM. A poor CPS-specific memory response was observed, with only a moderate boost in IgM titers and no IgG. Both protein-and CPS-specific Ab responses were Toll-like receptor 2 independent. By using S. suis type 2 strains of European or North American origin, the poor CPS-specific Ab response was demonstrated to be independent of the genotypic/phenotypic diversity of the strain within serotype 2. Finally, the CPS-specific Ab response was also impaired and lacked isotype switching in S. suis-infected pigs, the natural host of the bacterium. The better resistance of preinfected animals to reinfection with the same strain of S. suis type 2 might thus more likely be related to the development of a protein rather than CPS Ab response.

Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine

“…In contrast, S. suis serotype 2 CPS alone is unable to induce any significant antibody response, even when adjuvanted with TiterMax Gold or Stimune or when combined with the TLR ligand CpG in mice (unpublished results). Furthermore, previous studies using live S. suis serotype 2 infection showed modest IgM and no isotype-switched IgG anti-CPS antibody titers in pigs and in mice even after an experimental reinfection (17). Thus, S. suis serotype 2 CPS seems to be particularly nonimmunogenic, making it an ideal candidate for evaluation of the effect of glycoconjugation on immunogenicity.…”

“…All experiments involving mice were conducted in accordance with the guidelines and policies of the Canadian Council on Animal Care and the principles set forth in the Guide for the Care and Use of Laboratory Animals by the Animal Welfare Committee of the University of Montreal. Five-to 6-week-old C57BL/6 female mice (Charles River, Wilmington, MA), largely used for studies on S. suis pathogenesis (17,(33)(34)(35), were immunized subcutaneously with different doses of the S. suis CPS conjugate preparations (see Results) in 0.1 ml PBS on day 0 and boosted on day 21. In a first set of experiments aimed to compare different adjuvants, 3 groups (n ϭ 10) received 25 g of the 2:1 mixed conjugate dissolved in PBS adjuvanted with either 20 g of CpG oligodeoxyribonucleotide (ODN) 1826 (InvivoGen, San Diego, CA), Stimune (Prionics, La Vista, NE), or TiterMax Gold (CytRx Corporation, Norcross, GA) following the manufacturers' recommendations.…”

“…As the CPS is the most external bacterial layer in contact with the host, antibodies against it are highly opsonizing and protective, as demonstrated for several encapsulated pathogens (17)(18)(19)(20). Paradoxically, due to their carbohydrate nature, CPSs are in general considered poorly immunogenic and do not generate long-lasting adaptive immune responses.…”

Immunization with Streptococcus suis bacterin plus recombinant Sao protein in sows conveys passive immunity to their piglets

“…CPS is a poor immunogen due to its thymus-independent property and cannot induce sufficient immune response [8]. Study showed that coupling S. suis type 2 CPS to tetanus toxoid can induce T cell-dependent response, inducing IgM and IgGs for protection against challenges in mice and pigs [9, 10]. In addition, immunization with certain virulence factors, such as suilysin, muramidase-released protein (MRP) and extracellular factor (EF), has been demonstrated to protect pigs from challenge with homologous or heterologous strains of S. suis .…”

A capsular polysaccharide-expressing live vaccine suppresses streptococcal toxic shock-like syndrome and provides sequence type-independent protection during Streptococcus suis infection

“…As isotype-switched IgG plays an important role in the fight against encapsulated extracellular bacteria (35, 36), antibodies (Abs) to the entire encapsulated SC19 strain were assessed after 2015033 immunization. Immunized mice exhibited a significant increase in IgG, IgG1, and IgG2a, which remained at high levels until the end of the experiment, while mice injected with phosphate buffered saline (PBS) showed no detectable increases (Fig.…”