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

Abstract

dStreptococcus suis serotype 2 is an encapsulated bacterium and one of the most important bacterial pathogens in the porcine industry. Despite decades of research for an efficient vaccine, none is currently available. Based on the success achieved with other encapsulated pathogens, a glycoconjugate vaccine strategy was selected to elicit opsonizing anti-capsular polysaccharide (anti-CPS) IgG antibodies. In this work, glycoconjugate prototypes were prepared by coupling S. suis type 2 CPS to tetanus toxoid, and the immunological features of the postconjugation preparations were evaluated in vivo. In mice, experiments evaluating three different adjuvants showed that CpG oligodeoxyribonucleotide (ODN) induces very low levels of anti-CPS IgM antibodies, while the emulsifying adjuvants Stimune and TiterMax Gold both induced high levels of IgGs and IgM. Dose-response trials comparing free CPS with the conjugate vaccine showed that free CPS is nonimmunogenic independently of the dose used, while 25 g of the conjugate preparation was optimal in inducing high levels of anti-CPS IgGs postboost. With an opsonophagocytosis assay using murine whole blood, sera from immunized mice showed functional activity. Finally, the conjugate vaccine showed immunogenicity and induced protection in a swine challenge model. When conjugated and administered with emulsifying adjuvants, S. suis type 2 CPS is able to induce potent IgM and isotype-switched IgGs in mice and pigs, yielding functional activity in vitro and protection against a lethal challenge in vivo, all features of a T cell-dependent response. This study represents a proof of concept for the potential of glycoconjugate vaccines in veterinary medicine applications against invasive bacterial infections.

Porcine Dendritic Cells as an In Vitro Model to Assess the Immunological Behaviour of Streptococcus suis Subunit Vaccine Formulations and the Polarizing Effect of Adjuvants

“…However, the polarizing effect of this adjuvant after swine immunization has been poorly addressed [10]. A recently reported pig vaccination trial with the S. suis CPS-TT conjugate prototype adjuvanted in Stimune ® showed a preferential IgG1 isotype switch [15], confirming our in vitro observations with swine DCs. Studies in mice also showed that Stimune ® preferentially polarizes the humoral response towards the IgG1 class when combined with either a peptide antigen [63] or a glycoconjugate vaccine [64].…”

“…Stimune ® has been largely used in veterinary medicine, including swine vaccination trials against S. suis [10,15,61,62]. However, the polarizing effect of this adjuvant after swine immunization has been poorly addressed [10].…”

“…As indicated above, Stimune ® is a Marcol 52-based emulsion, and, when this mineral oil is used as adjuvant in combination with different S. suis immunogenic proteins, it has also been shown to induce a Th2-biased antibody response in mice [10]. In contrast, TiterMax Gold ® is a squalene-based adjuvant which has been reported to induce either mixed Th1/Th2 or Th2-polarized humoral responses in mice [15,65,66]. Squalene based oil-in-water emulsions (MF59 and AS03) licensed for human use also stimulate a mixed Th1/Th2 cell phenotype [26].…”

“…Nevertheless, immunization studies showed that protection conferred by enolase seems to depend on the adjuvant used in the vaccine formulation [12,13,14]. Similarly, it was recently reported that generation of protective antibodies after immunization with S. suis CPS as antigen was restricted to CPS conjugation to an immunogenic carrier protein and the use of emulsifying adjuvants [15]. CPS is a promising vaccine candidate because it is the antigen at the base of serotyping and thus can confer universal protection against all strains within the same serotype [10].…”

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 .…”