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Using data from ultra-low dose (ULD) infection of control and BCG-vaccinated mice, we developed mathematical models of Mycobacterium tuberculosis (Mtb) growth and dissemination between the lungs. Alternative direct and indirect dissemination pathways fit unvaccinated data equally well, indicating multiple plausible routes of spread. Best fit models predicted that BCG reduces the rate of Mtb dissemination between lungs by nearly 90% while only modestly reducing the replication rate by 9%. Interestingly, stochastic simulations of Mtb dynamics with early bacterial killing showed that a growth-reducing vaccine would result in fewer infected mice, lower lung CFU, and decreased bilateral infection of the lung even at relatively moderate efficacy levels. Further, we estimated sample sizes needed to detect vaccine effects in preclinical trials. This framework provides a quantitative, mechanistic basis for interpreting BCG efficacy and offers a framework for evaluating next-generation TB vaccines in the ULD infection model.<\/jats:p>","DOI":"10.64898\/2026.03.10.710600","type":"posted-content","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:00:12Z","timestamp":1773284412000},"source":"Crossref","is-referenced-by-count":0,"title":["BCG vaccination reduces the rate of Mycobacterium tuberculosis dissemination between murine lungs"],"prefix":"10.64898","author":[{"given":"Dipanjan","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Host-Pathogen Interactions (HPI) program, Texas Biomedical Research Institute, San Antonio, TX 78227, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6572-1691","authenticated-orcid":false,"given":"Vitaly V.","family":"Ganusov","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions (HPI) program, Texas Biomedical Research Institute, San Antonio, TX 78227, USA"},{"name":"Molecular Microbiology and Immunology department, University of Texas at San Antonio, San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026082704350820000_2026.03.10.710600v3.1","unstructured":"World Health Organization 2024 Global tuberculosis report. https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2024\/tb-disease-burden. 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