This chapter describes current efforts to develop safe and effective vaccines to prevent S. pyogenes infections. Although clinical development has been slow, there are a number of available approaches, based on a detailed understanding of the molecular pathogenesis of infection and protective immune responses in animals and humans. The development of M protein-based vaccines has taken full advantage of molecular techniques, rapid and reproducible emm typing methods, and modern molecular engineering that involves gene synthesis and scalable production. Common M epitopes have been engineered into a vaccine that contains a minimal B cell epitope to optimize functional antibody responses. Through genome-based reverse vaccinology, several common antigens have been identified as potential vaccine components. Although the global epidemiology of S. pyogenes infections is still not well defined, a growing amount of information is being used to inform vaccine design. As more vaccines enter clinical trials, there is a need to define common denominators in protocol design, particularly as they relate to safety assessments and efficacy.
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