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<p>A commercial vaccine to address the high global burden of Group A <i>Streptococcus</i> (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.</p>

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An mRNA vaccine encoding five conserved Group A Streptococcus antigens

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

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  • 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

摘要

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.