Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Sowmya Ajay Castro; Sarah Thomson; Helen Alexandra Shaw; Azul Zorzoli; Benjamin H. Meyer; Mark Reglinski; Mark McNeil; Helge C. Dorfmueller

doi:10.1016/j.jvacx.2025.100676

Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Sowmya Ajay Castro, Sarah Thomson, Helen Alexandra Shaw, Azul Zorzoli, Benjamin H. Meyer, Mark Reglinski, Mark McNeil, Helge C. Dorfmueller (Lead / Corresponding author)

Molecular Microbiology

Research output: Contribution to journal › Article › peer-review

1 Downloads (Pure)

Abstract

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, 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 were detected when re-stimulated with the immunogen RhaPS-OMV. We report the efficacy and potency of recombinant produced RhaPS triggering antibodies that recognise Strep A bacteria and facilitate monocyte dependent opsonophagocytosis of several Strep A serotypes.

Original language	English
Article number	100676
Number of pages	11
Journal	Vaccine
Volume	25
Early online date	11 Jun 2025
DOIs	https://doi.org/10.1016/j.jvacx.2025.100676
Publication status	E-pub ahead of print - 11 Jun 2025

Keywords

Streptococcus pyogenes
Group A Streptococcus
Group A Carbohydrate
Rhamnose
outer membrane vesicles
M protein, vaccine
Group a Streptococcus
Group a carbohydrate
Outer membrane vesicles
Vaccine
M protein

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jvacx.2025.100676Licence: CC BY

Final published versionFinal published version, 3.52 MBLicence: CC BY

Cite this

Ajay Castro, S., Thomson, S., Shaw, H. A., Zorzoli, A., Meyer, B. H., Reglinski, M., McNeil, M., & Dorfmueller, H. C. (2025). Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis. Vaccine, 25, Article 100676. Advance online publication. https://doi.org/10.1016/j.jvacx.2025.100676

@article{e514ecc002bb4d3294f7461229807855,

title = "Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis",

abstract = "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, 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 were detected when re-stimulated with the immunogen RhaPS-OMV. We report the efficacy and potency of recombinant produced RhaPS triggering antibodies that recognise Strep A bacteria and facilitate monocyte dependent opsonophagocytosis of several Strep A serotypes.",

keywords = "Streptococcus pyogenes, Group A Streptococcus, Group A Carbohydrate, Rhamnose, outer membrane vesicles, M protein, vaccine, Group a Streptococcus, Group a carbohydrate, Outer membrane vesicles, Vaccine, M protein",

author = "{Ajay Castro}, Sowmya and Sarah Thomson and Shaw, {Helen Alexandra} and Azul Zorzoli and Meyer, {Benjamin H.} and Mark Reglinski and Mark McNeil and Dorfmueller, {Helge C.}",

note = "Publisher Copyright: {\textcopyright} 2025",

year = "2025",

month = jun,

day = "11",

doi = "10.1016/j.jvacx.2025.100676",

language = "English",

volume = "25",

journal = "Vaccine",

issn = "1873-2518",

publisher = "Elsevier",

}

Ajay Castro, S , Thomson, S, Shaw, HA, Zorzoli, A, Meyer, BH, Reglinski, M, McNeil, M & Dorfmueller, HC 2025, 'Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis', Vaccine, vol. 25, 100676. https://doi.org/10.1016/j.jvacx.2025.100676

TY - JOUR

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 - McNeil, Mark

AU - Dorfmueller, Helge C.

PY - 2025/6/11

Y1 - 2025/6/11

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, 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 were detected when re-stimulated with the immunogen RhaPS-OMV. We report the efficacy and potency of recombinant produced RhaPS triggering antibodies that recognise Strep A bacteria and facilitate monocyte dependent opsonophagocytosis of several Strep A serotypes.

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, 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 were detected when re-stimulated with the immunogen RhaPS-OMV. We report the efficacy and potency of recombinant produced RhaPS triggering antibodies that recognise Strep A bacteria and facilitate monocyte dependent opsonophagocytosis of several Strep A serotypes.

KW - Streptococcus pyogenes

KW - Group A Streptococcus

KW - Group A Carbohydrate

KW - Rhamnose

KW - outer membrane vesicles

KW - M protein, vaccine

KW - Group a Streptococcus

KW - Group a carbohydrate

KW - Outer membrane vesicles

KW - Vaccine

KW - M protein

UR - http://www.scopus.com/inward/record.url?scp=105007684605&partnerID=8YFLogxK

U2 - 10.1016/j.jvacx.2025.100676

DO - 10.1016/j.jvacx.2025.100676

M3 - Article

SN - 1873-2518

VL - 25

JO - Vaccine

JF - Vaccine

M1 - 100676

ER -

Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Development of a universal Group A Streptococcus Glycoconjugate vaccine (joint with LSHTM)

Exploration of Biosynthetic Carbohydrates as Vaccine Candidates for Streptococcus Pyogenes

Functional and Structural Studies of the Streptococcal Virulence Factor Group A Carbohydrate Biosynthesis Pathway (Sir Henry Dale Fellowship)

Cite this

Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Development of a universal Group A Streptococcus Glycoconjugate vaccine (joint with LSHTM)

Exploration of Biosynthetic Carbohydrates as Vaccine Candidates for Streptococcus Pyogenes

Functional and Structural Studies of the Streptococcal Virulence Factor Group A Carbohydrate Biosynthesis Pathway (Sir Henry Dale Fellowship)

Research output

Cite this