TOWARDS A VACCINE FOR RHEUMATIC-FEVER - IDENTIFICATION OF A CONSERVEDTARGET EPITOPE ON M-PROTEIN OF GROUP-A STREPTOCOCCI

Rheumatic fever and rheumatic heart disease remain very common in deve loping countries, and a vaccine to protect against these disorders wou ld have a great impact on public health. A vaccine must target the M p rotein of group A streptococci (Streptococcus pyogenes), but until lat ely immunity was thought to be strain-specific and dependent on antibo dies to the variable serotype-specific regions of the protein. Experim ents in animals have suggested the conserved region of the M protein a s a possible alternative target for protective antibodies. We construc ted a 20-aminoacid peptide (peptide 145) within the conserved region o f the carboxyl terminus of the protein. In mice the peptide induced se rum antibodies that could opsonise reference type 5 streptococci. By e nzyme-linked immunosorbent assay, positive responses to peptide 145 we re obtained with serum from 77 (90%) of 86 Aboriginal subjects and 135 (81%) of 167 Thai subjects living in areas with high exposure to stre ptococci. Only 10 (14%) of 71 Caucasian subjects with low exposure to streptococci showed positive responses. There was no difference in the proportion positive between subjects with rheumatic heart disease and control groups (other or no heart disease). Antibodies to peptide 145 were able to opsonise isolates of streptococci from Aboriginal and Th ai subjects with acute rheumatic fever as well as reference strains. T his highly conserved part of the M protein may be a suitable target fo r vaccines to prevent steptococcal infections and their sequelae.