The high antigenic diversity of Streptococcus pyogenes (StrepA) presents extensive challenges to vaccine development, however cryptic epitopes—conserved across emm types—offer an alternative approach. Our group has developed two promising vaccine candidates combining modified synthetic M-protein epitopes (J8 or p*17) and K4S2, a non-M-protein epitope derived from the anti-neutrophil chemotaxis factor SpyCEP. These epitopes are individually conjugated to the carrier protein CRM197, combined, then formulated with aluminium hydroxide (Alum). The two final formulations, J8-CRM197+K4S2-CRM197/Alum and p*17-CRM197+K4S2-CRM197/Alum, are currently undergoing a Phase I clinical trial.
The trial was divided into two stages to maximise safety, involving a single-blind test dosing phase, and a placebo-controlled, double-blind randomised controlled trial. Intramuscular immunisations were administered at 0, 3 and 6 weeks. Following three immunisations with either vaccine, peptide-specific serum IgG titres increased 2-weeks and 6-months post third vaccination compared to pre-vaccination. Three immunisations with either vaccine also demonstrated induction of bactericidal antibodies against multiple StrepA strains (5448 and 2031) at 2-weeks post third vaccination compared to pre-vaccination, which was sustained and further increased at 6-months post third vaccination, despite an observed drop in peptide-specific antibody titres.
Results show our peptide-conjugate vaccines targeting highly conserved regions of the M protein and SpyCEP were shown to be safe in preclinical studies. Vaccination induced robust peptide-specific serum IgG responses that were sustained for at least six months post-final vaccination. Notably, the functional activity of vaccine-induced antibodies improved over time, suggesting a potential increase in antibody affinity.