Synthesis and Immunological Evaluation of M Protein Targeted Tetra-Valent and Tri-Valent Group A Streptococcal Vaccine Candidates Based on the Lipid-Core Peptide System

Abstract

Group A streptococcus (GAS) is responsible for causing many clinical complications including the relatively benign streptococcal pharyngitis and impetigo. However, if left untreated, these conditions may lead to more severe diseases such as rheumatic fever (RF) and rheumatic heart disease (RHD). These diseases exhibit high morbidity and mortality, particularly in developing countries and in indigenous populations of affluent countries. As RF and RHD only ever occur following GAS infection, a vaccine offers promise for their prevention. As such, we have investigated the use of the lipid-core peptide (LCP) system for the development of multi-valent prophylactic GAS vaccines. The current study has investigated the capacity of this system to adjuvant up to four different GAS peptide epitopes. Presented are the synthesis and immunological assessment of tetra-valent and tri-valent GAS LCP systems. We demonstrated their capacity to elicit systemic IgG antibody responses in B10.BR mice to all GAS peptide epitopes. The data also showed that the LCP systems were self-adjuvanting. These findings are particularly encouraging for the development of multi-valent LCP-based GAS vaccines.