Influence of intranasal immunization with synthetic peptides corresponding to conserved epitopes of M protein on mucosal colonization by group A streptococci

Abstract

A major virulence factor of group A streptococci is M protein, a surface-exposed fibrillar molecule of which there exist more than 80 distinct serological types. Antigenic variability resides largely in the amino-terminal region of M protein, whereas the carboxy-terminal half of the molecule is highly conserved among different M serotypes. We sought to determine whether mucosal immunization with conserved epitopes of M protein influences the course of mucosal colonization by group A streptococci in a mouse model. Synthetic peptides corresponding to sequences in the conserved region of M protein were covalently linked to the mucosal adjuvant cholera toxin B subunit. Mice were immunized intranasally with the peptide-cholera toxin B subunit conjugate or with cholera toxin B subunit alone and then challenged intranasally with live streptococci. Pharyngeal colonization by streptococci was measured for up to 15 days postchallenge. Mice immunized with synthetic peptides showed a significant reduction in colonization compared with the control group. The data demonstrate that immunity evoked by conserved portions of M protein influences the outcome of group A streptococcal infection at the nasopharyngeal mucosa in a mouse model.