An mRNA vaccine encoding five conserved Group A Streptococcus antigens
A commercial vaccine to address the high global burden of Group A Streptococcus (GAS) disease is an urgent and unmet medical need. Messenger RNA (mRNA) lipid-nanoparticle (LNP) vaccines represent a largely untapped platform for targeting bacterial pathogens. Here, we evaluate the immunogenicity and preclinical efficacy of a multicomponent mRNA-LNP vaccine formulation based on the GAS vaccine, Combo#5. Combo#5 mRNA-LNP antigens confer protection from infection in mouse intraperitoneal and subcutaneous challenge models. Combo#5 mRNA-LNP vaccination generates significantly increased frequencies and numbers of effector type CD4+ and CD8 + T cells in the spleen, enhances T follicular helper cells, germinal center B cells and memory B cells in the spleen and draining lymph nodes, and boosts the production of antigen-specific antibodies. These findings demonstrate the potential of the mRNA-LNP platform for the development of vaccines against bacterial pathogens.
Authors
- Shannon Green (ORCID: https://orcid.org/0000-0003-3446-5183)
- David M. P. De Oliveira (ORCID: https://orcid.org/0000-0002-5085-7163)
- Mark J. Walker (ORCID: https://orcid.org/0000-0001-7423-2769)
- Isabel Courtney
- Obadiah J. Plante
- Jinrui Na (ORCID: https://orcid.org/0000-0002-0134-5970)
- Steven J. Hancock (ORCID: https://orcid.org/0000-0001-7203-2640)
- Laura Davis
- Gayathiri Elangovan (ORCID: https://orcid.org/0000-0001-8858-639X)
- Amanda J. Cork (ORCID: https://orcid.org/0000-0003-2207-6877)
- Christina Dold (ORCID: https://orcid.org/0000-0003-2314-507X)
- Stephan Brouwer (ORCID: https://orcid.org/0000-0002-9777-2992)
- Ismail Sebina (ORCID: https://orcid.org/0000-0003-3232-3472)
- R. H. Bolton (ORCID: https://orcid.org/0000-0002-8407-7309)
- Johanna Richter (ORCID: https://orcid.org/0000-0002-2043-0003)
- Brody Pullinger (ORCID: https://orcid.org/0000-0001-7215-7865)
- Gabrielle T. Belz (ORCID: https://orcid.org/0000-0002-9660-9587)
- Bodie F. Curren (ORCID: https://orcid.org/0000-0002-1165-6406)
- Nichaela Harbison-Price (ORCID: https://orcid.org/0000-0002-5794-1923)
- Meredith B. Finn
- Ruby Pelingon (ORCID: https://orcid.org/0000-0001-7295-088X)
- Carmen Cuéllar (ORCID: https://orcid.org/0000-0001-7948-9889)
- Miguel Aguirre
- Örjan Ericsson
- Nia Bickham
Institutions
- The University of Queensland (AU)
- Moderna Therapeutics (United States) (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1038/s41467-025-60580-0
- Citations
- 6
- Primary Topic
- Streptococcal Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 11.27
Funders
- Fondation Leducq
- Medical Research Council
- National Health and Medical Research Council