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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1540359
This article is part of the Research Topic Vaccines and Molecular Therapeutics for Tuberculosis View all 3 articles

Novel mRNA vaccines induce potent immunogenicity and afford protection against tuberculosis

Provisionally accepted
Christopher De Voss Christopher De Voss Marcellus Korompis Marcellus Korompis Shuailin Li Shuailin Li Alberta Ateere Alberta Ateere Helen McShane Helen McShane Elena Stylianou Elena Stylianou *
  • Jenner Institute, Nuffield Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom

The final, formatted version of the article will be published soon.

    Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease with a severe global burden. The intractability of Mtb has prevented the identification of clear correlates of protection against TB and hindered the development of novel TB vaccines that are urgently required. Lipid nanoparticle (LNP)-formulated mRNA is a highly promising vaccine platform that has yet to be thoroughly applied to TB. We selected five Mtb antigens (PPE15, ESAT6, EspC, EsxI, MetE) and evaluated their potential as LNP-formulated mRNA vaccines, both when each antigen was delivered individually, and when all five antigens were combined in a single mix regimen (m-Mix). Each construct demonstrated unique cellular and humoral immunogenicity, and both m-Mix, as well as the single antigen EsxI, conferred significant protection in a murine Mtb challenge model. Whilst the potent immune responses of each mRNA were maintained when applied as a boost to BCG, there was no additional increase to the efficacy of BCG. Combination of m-Mix with a recombinant, replication-deficient chimpanzee adenovirus (ChAdOx1), in a heterologous prime-boost delivery (C-m-Mix), appeared to result in increased protection upon murine Mtb infection, than either regimen alone. This work warrants further investigation of LNP-formulated mRNA vaccines for TB, whilst indicating the potential of m-Mix and C-m-Mix to progress to further stages of vaccine development.

    Keywords: Tuberculosis1, Vaccines2, mRNA3, viral-vector4, BCG5

    Received: 05 Dec 2024; Accepted: 27 Jan 2025.

    Copyright: © 2025 De Voss, Korompis, Li, Ateere, McShane and Stylianou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Elena Stylianou, Jenner Institute, Nuffield Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.