Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine.
Streptococcus 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 μg 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.
Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
Guillaume
http://orcid.org/0000-0001-7158-9594
G
Goyette-Desjardins
Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
Cynthia
C
Calzas
Pharmaqam, Department of Chemistry, Université du Québec à Montréal, Montreal, Quebec, Canada.
Tze Chieh
TC
Shiao
Boehringer Ingelheim Vetmedica, Inc., St. Joseph, Missouri, USA.
Axel
A
Neubauer
Boehringer Ingelheim Vetmedica, Inc., St. Joseph, Missouri, USA.
Jennifer
J
Kempker
Pharmaqam, Department of Chemistry, Université du Québec à Montréal, Montreal, Quebec, Canada.
René
R
Roy
Laboratory of Research on Streptococcus suis, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
Marcelo
M
Gottschalk
Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada mariela.segura@umontreal.ca.
Mariela
M
Segura
D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology*; D005260:Female; D006001:Glycoconjugates / Q000276:immunology*; D007114:Immunization; D017578:Immunoglobulin Class Switching; D056747:Immunomodulation; D051379:Mice; D009838:Oligodeoxyribonucleotides; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D065288:Serogroup; D013290:Streptococcal Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D017011:Streptococcus suis / Q000145:classification / Q000276:immunology*; D013552:Swine; D018074:Vaccines, Conjugate / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D006001:Glycoconjugates; D009838:Oligodeoxyribonucleotides; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate