Protection Against Group A Streptococcus by Immunization with J8-diphtheria Toxoid: Contribution of J8- and Diphtheria Toxoid-specific Antibodies to Protection

A conformationally constrained, minimally conserved peptide from the M protein of group A streptococcus (GAS) has been defined. It consists of 12 amino acids from the C-repeat region within a non-M protein helix-forming sequence and is referred to as "J8." Here, we investigate the immunogenicity of a J8-diphtheria toxoid (DT) conjugate adjuvanted with the human-compatible adjuvants, SBAS2 and alum, and demonstrate that it is capable of inducing opsonic antibodies and can protect outbred mice from virulent challenge. In a range of experiments, protection correlated with the titer of J8-specific antibodies and not with the induction of J8-specific T cells. However, DT-specific antibodies (as well as J8-specific antibodies) were shown to stain the surface of fixed GAS and to be capable of opsonizing live organisms. DT may be an ideal carrier protein for J8 and other GAS peptides for GAS vaccines.