Rhamnose Polysaccharide-Decorated Outer Membrane Vesicles as a Vaccine Candidate Targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

TY - UNPB

T1 - Rhamnose Polysaccharide-Decorated Outer Membrane Vesicles as a Vaccine Candidate Targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

AU - Ajay Castro, Sowmya

AU - Thomson, Sarah

AU - Shaw, Helen Alexandra

AU - Zorzoli, Azul

AU - Meyer, Benjamin H

AU - Reglinski, Mark

AU - Dorfmueller, Helge

PY - 2024/8/23

Y1 - 2024/8/23

N2 - Group 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 on E. coli outer 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) in S. pyogenes and the newly emerged S. dysgalactiae subsp. 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.

AB - Group 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 on E. coli outer 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) in S. pyogenes and the newly emerged S. dysgalactiae subsp. 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.

KW - Streptococcus pyogenes

KW - Group A Streptococcus

KW - Group A Carbohydrate

KW - Rhamnose

KW - outer membrane vesicles

KW - M protein, vaccine

U2 - 10.1101/2024.08.23.609347

DO - 10.1101/2024.08.23.609347

M3 - Preprint

BT - Rhamnose Polysaccharide-Decorated Outer Membrane Vesicles as a Vaccine Candidate Targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

PB - BioRxiv

ER -