Prospecting for new group A streptococcal vaccine candidates

Most group A streptococcal (GAS) vaccine strategies focused on the surface M protein of the GAS. However, vaccine based on M protein have some drawbacks. In the present study, we used two approaches to identify new proteins and peptides that may have utility as vaccine candidates.

A whole gel elution procedure was used to separate GAS surface antigens into 9 size fractionated pools. Mice were vaccinated with each pool and antibody titre, opsonic ability and protective capacity measured. In an alternative approach BioInformatics was used to identify putative GAS surface proteins. Peptides from within these proteins were then selected on the basis of predicted antigenicity or location. These peptides were conjugated to keyhole lymphocyanin (KLH) and immunogenicity measured in a mouse model.

One pool of GAS surface proteins (approximately 29kDa) induced antibodies that were both opsonic and potentially protective. Immunoflourescent microscopy demonstrated that these antibodies bound to the surface of M1 GAS. Amino acid sequencing subsequently identified superoxide dismutase as the major antigen in this pool. A BioInformatic search of the M1 GAS genome and subsequent analysis identified several peptides that fulfilled criteria as potential vaccine candidates. Each peptide when conjugated to KLH was able to induce a strong antibody response.

Several new antigens were identified that may have potential as vaccine targets. A future GAS vaccine may have multiple peptide epitopes, providing protection against multiple GAS strains.