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 designed to protect against multiple StrepA strains infections. These vaccines incorporate modified synthetic M-protein epitopes (J8 or p*17) and a non-M-protein epitope derived from the anti-neutrophil chemotaxis factor SpyCEP (K4S2). These epitopes are conjugated to the carrier protein CRM197 and formulated with aluminium hydroxide (Alum) to produce the final formulations: J8-CRM + K4S2-CRM/Alum and p*17-CRM + K4S2-CRM/Alum.
These vaccines are currently in use in a Phase I Clinical trial. Human volunteers received 3 doses of either vaccine candidate at 0, 3 and 6 weeks in a single-blinded sentinel study. Antibody titres and functional responses were assessed at either or both 2 weeks and 6 months after final immunisation. J8- and p*17-specific IgG titres were increased at both time points in participants vaccinated with either J8-CRM + K4S2-CRM/Alum or p*17-CRM + K4S2-CRM/Alum, respectively, compared to pre-vaccinated levels. Competition binding assays showed human vaccine-induced antibodies bound the surface of live StrepA in recipients of either vaccine. Functional opsonic activity assessment using a modified opsonophagocytic killing assay demonstrated induction of bactericidal activity at both time points. Previous research has shown only antibodies targeting the N-terminal region, and not the conserved central region, exhibit opsonic activity.
These findings, particularly those demonstrating bactericidal activity, are significant, and highlight the potential for continued use of these vaccine candidates in our Phase Ib study.