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bioRxiv · 10.1101/2025.09.30.679428

mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well-tolerated and efficacious in rodent models

Agrawal, N.·Ates, L. S.·Schille, S.·Chaturvedi, A.·Vogt, J.·Vukovic, N.·Vogel, A.·Diekmann, J.·Diken, M.·Sahin, U.
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Abstract

We designed and preclinically tested two mRNA-LNP-based vaccine candidates to protect against tuberculosis (TB). BNT164a1 and BNT164b1 encode the same eight Mycobacterium tuberculosis (Mtb) antigens expressed across different infection stages: Ag85A, Hrp1, ESAT-6, RpfD, RpfA, HbhA, M72, and VapB47. BNT164a1 utilizes nucleoside-unmodified mRNA, while BNT164b1 utilizes N1-methyl pseudouridine-modified mRNA. Prime-boost immunization with BNT164 candidates elicited antibody and/or T-cell responses against all antigens in three mouse strains (C57BL/6, BALB/c, and HLA-A2.1/DR1 humanized mice). The candidates demonstrated favorable safety profiles in a rat toxicity study and significantly reduced bacterial burdens of two Mtb strains in murine aerosol challenge models. BNT164 protection correlated with granuloma infiltration by CD8+ T cells with memory precursor phenotypes. In conclusion, BNT164a1 and BNT164b1 were immunogenic, well tolerated and efficacious in preclinical models and are the first mRNA-based TB vaccines to enter phase I/II clinical trials (NCT05537038, NCT05547464).

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Agrawal, N., Ates, L. S., Schille, S., Chaturvedi, A., Vogt, J., Vukovic, N., Vogel, A., Diekmann, J., Diken, M., Sahin, U.. 2025-10-01. mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well-tolerated and efficacious in rodent models. https://doi.org/10.1101/2025.09.30.679428

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