Synthetic peptide vaccine against mucosal colonization by group A streptococci. I. Protection against a heterologous M serotype with shared C repeat region epitopes

Abstract

M protein is an antigenically variable virulence determinant present on the surface of group A streptococci, and it provides the basis for the serologic typing scheme. Type-specific serum antibodies afford strong protection against infection by the homologous serotype. Non-type-specific antigenic epitopes also exist within the surface-exposed portion of M protein. Previous studies demonstrated that intranasal immunization with Ag corresponding to sequences within the non-type-specific pepsin-susceptible site and adjacent C repeat regions of M6 protein, evoke protective immunity against pharyngeal colonization by type 6 streptococci in a mouse model. Although the protective immunogens are not type-specific, the pepsin site region of M6 is shared among less than 20% of serotypes examined. Therefore it was necessary to determine whether more highly conserved M protein epitopes elicit mucosal protection against group A streptococci, and if protective immunity extends to heterologous serotypes. In this report, peptides were synthesized that correspond to sequences completely contained within the highly conserved C repeat region of M6 protein. Peptide Ag were covalently coupled to the mucosal adjuvant, cholera toxin B subunit (CTB), and mice immunized intranasally and orally with peptide-CTB conjugates were compared to control groups that received CTB only. Immunization with the peptide-CTB conjugates led to significant protection against pharyngeal colonization by group A streptococci. Furthermore, protection was observed against the heterologous M serotype, type 14. These findings suggest that protection against multiple serotypes of group A streptococci can be achieved with a vaccine consisting of the widely shared C repeat region of M6 protein.