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. 2025 Jun 17:jiaf277.
doi: 10.1093/infdis/jiaf277. Online ahead of print.

Sex Differences in Vaccine-Induced Immunity and Protection Against Mycobacterium tuberculosis

Gishnu Harikumar Parvathy  1 , David Hertz  1 , Dhananjay Bhandiwad  2   3 , Lars Eggers  1 , Linda von Borstel  1 , Jochen Behrends  4 , Martina Hein  4 , Viola Dreyer  5   6 , Jaqueline Marschner  1 , Zane Orinska  7   8 , Stefan Niemann  5   6 , Stefan H E Kaufmann  9   10   11 , Torsten Goldmann  8   12 , Hanna Lotter  13 , Mario Alberto Flores-Valdez  14 , Bianca E Schneider  1
Affiliations

Sex Differences in Vaccine-Induced Immunity and Protection Against Mycobacterium tuberculosis

Gishnu Harikumar Parvathy et al. J Infect Dis. .

Abstract

Tuberculosis (TB) remains a leading global cause of death, with approximately 1.3 million fatalities annually. While males are more susceptible to TB, the underlying immune differences and their impact on vaccine efficacy are not fully understood. In this study, we vaccinated male and female C57BL/6 mice with BCG and 2 recombinant derivatives, VPM1002 and BCGΔBCG1419c, and assessed their protection against Mycobacterium tuberculosis (Mtb) HN878. While all 3 vaccines showed comparable efficacy in females, BCG did not protect males from Mtb-induced death. Instead, recombinant vaccines provided improved protection in males. Vaccination of males with BCGΔBCG1419c, but not BCG, enhanced CD8 T-cell and B-cell recall responses in vaccine-draining lymph nodes, and reduced lung inflammation after Mtb challenge. These findings underscore the impact of sex differences on vaccine efficacy and suggest that future research should consider sex as a biological variable to optimize TB vaccination strategies.

Keywords: Mycobacterium tuberculosis; BCG; mouse model; sex differences; vaccination.

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Conflict of interest statement

Potential conflicts of interest. S. H. E. K. is co-inventor and co-holder of a patent for the TB vaccine VPM1002, which has been licensed to Vakzine Projekt Management GmbH and Serum Institute of India Ltd. M. A. F.-V. has a patent issued for the BCGΔBCG1419c as vaccine candidate against TB. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.