Background
Streptococcus pyogenes is a human-specific pathogen that colonizes the skin and nasopharynx of over 600 million people every year. Consequences of repeated nasopharyngeal infection are two-fold. While a protective immune response is initially established, autoimmune sequelae may develop following increasing numbers of unresolved infections. The existence of a protective immune response has been anecdotally known for years; however, exact correlates of protective immunity remain unknown.
Methods
To investigate correlates of immunity following nasopharyngeal infection by S. pyogenes in an immunologically relevant environment, our laboratory uses a superantigen-sensitive, transgenic mouse model in which C57BL/6 mice express human MHC class II molecules.
Results
Using this model, we have found that mice exposed to three nasopharyngeal infections by S. pyogenes have a significantly lower bacterial burden in their nasal turbinates 48 hours post-infection compared to mice that received only one infection. Surprisingly, we found no antibodies to the streptococcal cell wall in mice infected either one or three times with S. pyogenes as per western blot, nor were there substantial titres to streptococcal antigens as measured by ELISA. Germinal center B cell responses were assessed via flow cytometry in mice that received intranasal superantigen protein vaccines. We found a significant decrease in germinal center B cells in mice that received an active superantigen vaccine compared to mice receiving an inactive version of the same superantigen.
Conclusion
Overall, understanding correlates of immunity is essential to the development of future vaccines and may eventually aid in our understanding of how S. pyogenes triggers autoimmunity.