Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus.

Abstract

Conserved protein antigens among serotypes of group A Streptococcus pyogenes (GAS) have been focused for vaccine development because of the diversity of GAS serotypes and risks of autoimmunity post-GAS infection. Precise delineation of protective immune response to each of GAS antigens is critical for vaccine efficacy and safety. We recently reported that immunization with SrtA of GAS provides Th17-dependent clearance of heterologous serotypes of GAS in NALT. SCPA is a surface virulence molecule of GAS and known to induce antibody-mediated protection against GAS. We hypothesized that co-immunization with SrtA and SCPA would provide more efficient protection by eliciting combined Th17 and antibody responses. The present study showed that mice that were intranasally co-immunized with SrtA/SCPA cleared GAS more efficiently than the mice that were immunized with either SrtA or SCPA individually, and as efficient as the mice that experienced repeated GAS infections. The co-immunization induced Th17 and robust SCPA antibody responses, accompanied by a rapid influx of neutrophils and high myeloperoxidase activity in NALT, suggesting that simultaneous induction of mucosal Th17 and neutralizing antibody responses offers more effective GAS elimination through rapid infiltration and activation of neutrophils. Moreover, Th17 response was strongly induced in mice that experienced repeated GAS-infection and maintained at a high level even after the bacteria were cleared; whereas, it was moderately induced and promptly returned to baseline following bacterial elimination in SrtA/SCPA co-immunized mice. Additional results showed that the survival rate of systemic challenge was significantly higher in infection experienced than in co-immunized mice, indicating that more immune elements are required for protection against systemic than mucosal GAS infection.