A safe and broadly protective vaccine against Group A Streptococcus (Strep A) is urgently needed to reduce the incidence and severity of superficial infections (e.g., pharyngitis and impetigo) and consequently to reduce i) the associated antibiotic prescriptions that may result in emergence of antimicrobial resistance and bystander selective pressure on human microbiome; and ii) the global burden of associated sequelae: acute rheumatic fever (ARF) and rheumatic heart disease (RHD). In order to achieve this goal, GVGH is developing a Strep A vaccine composed of 3 recombinant proteins (SLO, SpyAD and SpyCEP) and 1 glycoconjugate (Group A carbohydrate conjugated to recombinant CRM) formulated on aluminum hydroxide. When tested in mice, alum-based formulations induced a higher immune response (either in terms of antibody level, functionality, and cellular response) compared to the antigens in the absence of adjuvant, suggesting the need of the adjuvant for an effective Strep A vaccine. The high immunogenicity, as well as the affinity and functionality of antibodies raised by the adjuvanted vaccine have been confirmed also in rabbits and rats. Based on these results, we plan to progress the development of an adjuvanted vaccine to a Phase 1 dose-escalation clinical study to evaluate the safety and the immunogenicity profiles of the 4-component Strep A vaccine in Australian healthy adults.
MC, LM, FC, EC contributed equally to the work