BCG vaccination reduces growth and dissemination rates of Mycobacterium tuberculosis in ultra-low dose-infected mice 2996

Abstract Description BCG vaccine is the only licensed vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb). Even though billions of individuals have been vaccinated with BCG, efficacy of BCG vaccine and mechanisms by which it provides protection remain poorly understood. In a recent study, Plumlee et al PLoS Pathogens 2023 infected over a thousand of mice, about half of which were vaccinated with BCG, with ultra-low dose (ULD) of Mtb (about 1 bacterium/mouse). We developed several alternative mathematical models describing Mtb dynamics in the initially infected lung (named Lung 1) and Mtb dissemination to the collateral lung (Lung 2) and fitted these models to the data from Plumlee et al. experiments. Interestingly, alternative models assuming Mtb dissemination between the lungs directly or via an intermediate tissue (e.g., blood and/or spleen) describe the data on Mtb dynamics in unvaccinated mice with similar quality. In both models, we predict that Mtb replicates rapidly early during the infection, is controlled 1-2 months post-infection, but then resumes replication in the chronic phase. By fitting the models to Mtb dissemination data in BCG-vaccinated mice we found that the data are best explained if the vaccine reduces both the rate of Mtb replication in the lungs (by 9%) and the rate of Mtb dissemination between the lungs (by 85%). Our approach can be used to rigorously quantify efficacy of other TB vaccines in ULD-infected mice. Funding Sources NIH/NIAID R01AI158963 Topic Categories Vaccines and Immunotherapy (VAC)