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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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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