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

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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	Published - Aug 2025

UN SDGs

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

SDG 3 Good Health and Well-being

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

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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. https://doi.org/10.1016/j.jvacx.2025.100676

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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.\}",

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

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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 - 2025/8

Y1 - 2025/8

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

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DO - 10.1016/j.jvacx.2025.100676

M3 - Article

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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

UN SDGs

Keywords

ASJC Scopus subject areas

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)

Corrigendum to: “Rhamnose polysaccharide-decorated outer membrane vesicles as a vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis” (Vaccine: X, (2025), 25, C, (100676), (S2590136225000701), 10.1016/j.jvacx.2025.100676)