The GSK Vaccines Institute for Global Health is developing an M-free adjuvanted vaccine targeting conserved antigens comprising three recombinant proteins: Streptolysin O (Slo), S. pyogenes cell envelope protein (SpyCEP), S. pyogenes adhesion and division protein (SpyAD), and group A carbohydrate (GAC) conjugated to the CRM197 protein. Preclinical and toxicological results showed the candidate vaccine has an acceptable safety profile, is immunogenic, and able to induce a functional response against the target antigens in animals, encouraging the progression to Phase 1 dose-escalation clinical trial in Australian healthy adults.
Since a correlate of protection is not available yet, in preparation to assess the vaccine's immunogenicity in humans, we have developed and characterised in terms of specificity, precision, linearity, and repeatability several immunoassays.
A bead-based assay has been developed to simultaneously quantify IgG for each vaccine antigen, whereas assays looking at inhibition of various effector functions of the pathogen or its killing will enable to assess the functionality of the antibodies. This includes haemolysis inhibition assays for IgG antibodies against SLO, IL-8 inhibition cleavage assays for SpyCEP-targeted antibodies, adhesion-like inhibition assays for the SpyAD component, and a FACS-based THP-1 phagocytosis assay (OPA) as well as a CFU-based opsonophagocytosis killing (OPK) assay using HL-60 to evaluate antibody effectiveness against membrane antigens such as SpyAD, SpyCEP, and notably the GAC carbohydrate.
These assays will offer crucial insights to the clinical development of the candidate vaccine, characterizing IgG responses against anti-StrepA antigens and assessing antibody functionality in neutralizing StrepA or disrupting immune evasion mechanisms.