Rhamnose Polysaccharide-Decorated Outer Membrane Vesicles as a Vaccine Candidate Targeting Group A Streptococcus fromStreptococcus pyogenesandStreptococcus dysgalactiaesubsp.equisimilis

Abstract

AbstractGroup A Streptococcus (Strep A) cause a wide range of human-exclusive infections, annually killing more than 500,000 people. Antibiotic resistance incidence of invasive Strep A tripled in the past decade and emphasises the need to develop a universal Strep A vaccine. In this study, we developed recombinant rhamnose polysaccharides (RhaPS), a validated universal Strep A vaccine candidate, presented onE. coliouter membrane vesicles (OMVs). We investigated OMV-RhaPS for their immunogenicity in the mouse and rabbit models. Through flow cytometry, ELISA, Luminex assays, and immunofluorescence microscopy, we demonstrated that RhaPS-specific antibodies recognise Strep A strains via the Group A Carbohydrate (GAC) inS. pyogenesand the newly emergedS. dysgalactiaesubsp.equisimilis. Elevated IL-17a levels from RhaPS-OMV-immunised splenocytes indicate the RhaPS-specific stimulation of long-term memory immune cells. We are the first to report the efficacy and potency of recombinant produced RhaPS inducing humoral-mediated immune responses and triggering antibodies that recognise Strep A bacteria.