Journal article
Novel mRNA vaccines induce potent immunogenicity and afford protection against tuberculosis
- Abstract:
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Introduction: 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.
Methods: 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 mix regimen (m-Mix).
Results: Each mRNA 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.
Discussion: 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.5MB, Terms of use)
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- Publisher copy:
- 10.3389/fimmu.2025.1540359
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Immunology More from this journal
- Volume:
- 16
- Article number:
- 1540359
- Publication date:
- 2025-02-13
- Acceptance date:
- 2025-01-27
- DOI:
- EISSN:
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1664-3224
- Pmid:
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40018046
- Language:
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English
- Keywords:
- Pubs id:
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2092157
- Local pid:
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pubs:2092157
- Deposit date:
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2025-03-14
- ARK identifier:
Terms of use
- Copyright holder:
- De Voss et al.
- Copyright date:
- 2025
- Rights statement:
- 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) and the copyright owner(s) 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.
- Licence:
- CC Attribution (CC BY)
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