Structure-guided design of a broadly cross-reactive multivalent group a streptococcal vaccine

Vaccine. 2023 Aug 16:S0264-410X(23)00958-1. doi: 10.1016/j.vaccine.2023.08.026. Online ahead of print.ABSTRACTThe M protein of group A streptococci (Strep A) is a major virulence determinant and protective antigen. The N-terminal region of the M protein is variable in sequence, defines the M/emm type, and contains epitopes that elicit opsonic antibodies that protect animals from challenge infections. Although there are >200 M types of Strep A, there is now evidence that structurally related M proteins can be grouped into clusters and that immunity may be cluster-specific in addition to M type-specific. This observation has led to recent studies of structure-based design of multivalent M peptide vaccines to select peptides predicted to cross-react with heterologous M types to improve vaccine coverage. In the current study, we have applied a refined series of peptide structural algorithms to predict immunological cross-reactivity among 117 N-terminal M peptides representing the most prevalent M types of Strep A. Based on the results of the structural analyses, in combination with global M type prevalence data, we constructed a 32-valent vaccine containing 19 cross-reactive vaccine candidates predicted to cross-react with 37 heterologous M peptides to which were added 13 type-specific M peptides. The 4-protein recombinant vaccine was immunogenic in rabbits and elicited significant levels of antibodies against 31/32 (97%) vaccine peptides and 28/37 (76%) peptides predicted to ...
Source: Vaccine - Category: Allergy & Immunology Authors: Source Type: research