Streptococcus pyogenes is a Gram-positive bacterial pathogen of humans. It causes a broad range of disease from self-limiting throat and skin infections, to life-threatening streptococcal toxic shock syndrome and rheumatic heart disease resulting in over 500 000 deaths annually. Global efforts have been aimed at the development of a vaccine, but large serotypic diversity and the potential for autoimmune cross-reactivity have impeded this development. Current vaccine efforts are yet to define a single vaccine to protect against both skin and mucosal infections. In humans, natural immunity is slow to develop and its role in preventing S.pyogenes infections is poorly understood. In addition, there is a need to understand the mechanism of cross-compartment immunity in S.pyogenes infections to aid in guiding vaccine development to protect from multiple serotypes and infection sites.
Through multiple sequential infections, we modelled repeated natural exposure to S.pyogenes in mice. We analysed bacterial load following each infection and screened for antibodies and antibody-secreting cells using ELISA and ELISPOT respectively. Using cytokine analysis and flow cytometry we aim to dissect the immune mechanisms involved in the development of immunity.
Following four homologous infections, while no circulating antibodies were detected, an increase in antibody secreting cells compared to naïve mice was observed. While assessing bacterial load, we determined that multiple sequential infections using a homologous isolate result in not only site-specific protection but also cross-compartment protection. Ongoing studies will investigate the effect of sequential heterologous infections on the development of immunity to multiple S.pyogenes strains.