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2025

Nat Commun. 2025 Jul 1;16(1):5439. doi: 10.1038/s41467-025-60580-0.

An mRNA vaccine encoding five conserved Group A Streptococcus antigens

Nichaela Harbison-Price, Ismail Sebina, Rhiannon A Bolton, Meredith Finn, Amanda J Cork, Isabel G Courtney, Steven Hancock, Ruby Pelingon, Johanna Richter, Olivia Ericsson, Shannon Green, Celeste Cuellar, Laura Davis, Brody Pullinger, Jack Na, Gayathiri Elangovan, David M P De Oliveira, Bodie F Curren, Nia Bickham, Miguel Aguirre, Christina Dold, Stephan Brouwer, Obadiah Plante, Gabrielle T Belz, Mark J Walker

Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. Frazer Institute, The University of Queensland, Brisbane, QLD, Australia. Moderna TX, 325 Binney Street, Cambridge, MA, USA. Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. Contributed equally.

Service type: Stock strains

Abstract

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.

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