Weaker protection against tuberculosis in BCG-vaccinated male 129 S2 mice compared to females. Issue 50 (8th December 2021)

• Record Type: Journal Article
• Authors: Nieuwenhuizen, Natalie E.; Zyla, Joanna; Zedler, Ulrike; Bandermann, Silke; Abu Abed, Ulrike; Brinkmann, Volker; Kaufmann, Stefan H.E.
• Is Part Of: Vaccine. Volume 39:Issue 50(2021)
• Page Start: 7253
• Page End: 7264
• Publication Date: 2021-12-08
• Subjects: BCG -- Tuberculosis -- Vaccination -- Sex differences -- T cells; TB tuberculosis -- Mtb Mycobacterium tuberculosis -- BCG Mycobacterium bovis Bacille Calmette-Guérin -- CFUs colony forming units -- PBS phosphate-buffered saline -- TRM resident memory T cells -- TEM effector memory T cells -- TCM central memory T cells -- PCA principal component analysis -- HC Hierarchical clustering -- MLR monocyte-to-lymphocyte ratio -- MTR myeloid-cell-to-T-cell-ratio -- PBMCs peripheral blood mononuclear cells; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.09.039
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Protective efficacy of BCG was weaker in male 129 S2 mice than in females. Male mice showed increased myeloid cell infiltration into lungs. T cell responses were weaker in male mice. Thus, sex plays a critical role in this experimental model of tuberculosis. Abstract: BCG – the only available vaccine against tuberculosis (TB) - was first given to babies 100 years ago in 1921. While it is effective against TB meningitis and disseminated TB, its efficacy against pulmonary TB is variable, notably in adults and adolescents. TB remains one of the world's leading health problems, with a higher prevalence among men. Male sex is associated with increased susceptibility to Mycobacterium tuberculosis in mice, but sex-specific responses to BCG vaccination have not been examined. In this study we vaccinated TB-susceptible 129 S2 mice with BCG and challenged with low-dose M. tuberculosis H37Rv by aerosol infection. BCG was protective against TB in both sexes, as unvaccinated mice lost weight more rapidly than vaccinated ones and suffered from worse lung pathology. However, female mice were better protected than males, showing lower lung bacterial burdens and less weight loss. Overall, vaccinated female mice had increased numbers of T cells and less myeloid cells in the lungs compared to vaccinated males. Principal component analysis of measured features revealed that mice grouped according to timepoint, sex and vaccination status. The features that had the biggest impact on grouping overall included numbers of CD8 T cells, CD8 central memory T cells and CD4 T effector cells, with neutrophil and CD11b + GR-1 − cell numbers having a big impact at day 29. Hierarchical clustering confirmed that the main difference in global immune response was due to mouse sex, with only a few misgrouped mice. In conclusion, we found sex-specific differences in response to M. tuberculosis H37Rv -challenge in BCG-vaccinated 129 S2 mice. This highlights the need to include both male and female mice in preclinical testing of vaccine candidates.