Streptococcus pyogenes infections remain a health problem in multiple countries because of poststreptococcal sequelae, such as rheumatic fever and rheumatic heart disease. The epidemiological growth of streptococcal diseases in undeveloped and developing countries has encouraged many groups to study vaccine candidates for preventing group A streptococcus infections. We developed a vaccine epitope (StreptInCor) composed of 55 amino acid residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. Using human blood samples, we showed that the StreptInCor epitope is recognized by individuals bearing different HLA class II molecules and could be considered a universal vaccine epitope. In addition, the StreptInCor molecular structure was solved by nuclear magnetic resonance spectroscopy, and a series of structural stability experiments was performed to elucidate its folding/unfolding mechanism. Using BALB-c and HLA class II transgenic mice, we evaluated the immune response over an extended period and found that StreptInCor was able to induce a robust immune response in both models. No cross-reaction was observed against cardiac proteins. The safety of the vaccine epitope was evaluated by analyzing histopathology, and no autoimmune or pathological reactions were observed in the heart or other organs. Vaccinated BALB/c mice challenged with a virulent strain of S. pyogenes had 100 % survival over 30 days. Taking all results into account, StreptInCor could be a safe and effective vaccine against streptococcus-induced disease.
Keywords: HLA class II transgenic mice; M protein; Rheumatic fever; Rheumatic heart disease; Streptococcus pyogenes; T and B cells; Vaccine.