Summary
Group A Streptococcus (GAS) is a human-exclusive bacterial pathogen killing more than 650,000 people annually, and no licensed vaccine exists. GAS bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydrate, which contains a rhamnose polysaccharide (RhaPS) backbone. We engineered the Group A Carbohydrate biosynthesis pathway to enable recombinant production using the industry standard route to couple RhaPS to selected carrier proteins within E. coli. Purified RhaPS-glycoconjugates elicited specific antibodies in mice and rabbits and bound to the surface of multiple GAS strains of diverse M-types, confirming the recombinantly produced RhaPS-glycoconjugates as valuable vaccine candidates. An efficient immunogenicity of antigens/vaccines requires suitable adjuvants. We found immunogenicity of polysaccharide vaccines that lack adjuvants is primarily due to the presence of Toll-like receptor (TLR) ligands, and that both antigen receptor and TLR signalling are essential for the antibody responses in vivo. Based on this rationale, we have developed a monophosphoryl lipid A (a TLR4-ligand)-based adjuvant formulation named Turbo. When adjuvanted with Turbo, FDA-approved or WHO-prequalified vaccines induced high levels of IgG of all isotypes across all ages of mice, minimised booster requirements, and prolonged the antibody responses for at least one year in mice, suggesting that Turbo as an adjuvant promotes durable and polyfunctional antibodies and maximise the efficacy of a vaccine. The goal of this proposal is to test the immunogenicity of RhaPS-glycoconjugates adjuvanted with Turbo or Alum, a widely used adjuvant as a comparator in infant and adult mice.
Project Outcomes
This study evaluated the immune response generated by different formulations of a glycoconjugate vaccine in mice. The vaccine contained a key protein (Protein1-RhaPS) and was tested with two different adjuvants—Alum and Turbo—to assess their effectiveness in enhancing immunity. The main focus was to investigate the generation of antibodies against the vaccine candidate and the activation of cytokines in spleen restimulation assays. In summary, both adjuvants produce vaccine specific antibodies, and our data revealed that the Turbo adjuvant may induce cell-mediated immunity, thereby potentially triggering the activation of memory cells.