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BNT164: Preclinical development of two mRNA-based tuberculosis vaccine candidates

S Schille*(1) N Agrawal *(1) A Chaturvedi(2) J Vogt(1) N Vukovic(1) L S Ates(1) A Vogel(1) J Diekmann(2) M Diken(2) U Sahin(3)

1:Immunotherapies and Preclinical Research, BioNTech SE, 55131 Mainz; 2:Non-Clinical Safety & DMPK, BioNTech SE, 55131 Mainz; 3:BioNTech SE, 55131 Mainz

* Both authors contributed equally

There is a critical need for new Tuberculosis (TB) vaccines to reduce the incidence and mortality of TB. BNT164a1 and BNT164b1 are two lipid-nanoparticle-formulated mRNA-based TB vaccine candidates. Both candidates encode the same combination of eight Mycobacterium tuberculosis (Mtb) antigens expressed across different stages of Mtb infection and only differ in the type of mRNA used (nucleoside-unmodified RNA or N1-methyl pseudouridine-containing modified RNA). Here, we report the immunogenicity, safety, and efficacy of BNT164a1 and BNT164b1 in preclinical animal models. Following prime-boost immunization, both BNT164 candidates elicited T-cell responses (CD4+ and/or CD8+) against each of the eight Mtb antigens in tested mouse strains (C57BL/6, BALB/c, and HLA-A2.1/DR1 humanized mice) as assessed by IFNy ELISpot. IgG responses were induced against six of the eight target antigens. BNT164 immunization significantly reduced bacterial burden in a low dose aerosol challenge Mtb infection model in C57BL/6 mice. In a GLP-compliant toxicology study in rats, the candidates showed a favorable safety profile.

In conclusion, BNT164a1 and BNT164b1 are immunogenic, efficacious, and well tolerated in preclinical models, and are the first mRNA-based TB vaccines to enter Phase I clinical trials (NCT05537038, NCT05547464).

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