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- W4385685754 abstract "Abstract Tuberculosis (TB) causes 1.6 million deaths annually and the standard human vaccine, intradermal (ID) Bacille-Calmette Guérin (BCG), does not prevent pulmonary TB. Previously, we showed that intravenous (IV) BCG immunization elicited robust TB-specific lung-resident T cell responses compared to ID BCG in rhesus macaques (RMs). Following Mycobacterium tuberculosis (Mtb) challenge, 6 out of 10 RMs had no detectable disease as demonstrated by bacterial burden, granuloma formation, and primary Mtb-specific immune responses. Together, these data suggest that Mtb is cleared rapidly from the lungs of IV BCG-vaccinated RMs. To investigate the vaccine-induced lung environment and anamnestic response that might mediate protection against Mtb early after challenge, we developed a high-dose Mtb infection model in RMs that allowed us to locate and live-image areas of Mtb infection in the lungs using confocal microscopy. RMs immunized for 5 months with either IV or ID BCG were challenged with Mtb Erdman mCherry and euthanized 4 or 11 days later to characterize the lung microenvironment. We observed reductions in bacterial burdens in the lungs of RMs that received IV BCG compared to ID BCG-vaccinated and unvaccinated controls by CFU plating, flow cytometry, and confocal microscopy despite using a high challenge dose. Increased T cells were quantified in the lungs of both IV and ID BCG-vaccinated RMs compared to unvaccinated controls by flow cytometry and confocal microscopy. This research provides an opportunity to mine immune correlates of protection in a preclinical model, at the site of infection, and at a post-challenge time point that has been minimally characterized. NIH Intramural Program" @default.
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- W4385685754 date "2023-05-01" @default.
- W4385685754 modified "2023-09-27" @default.
- W4385685754 title "Visualizing the early immune response to <i>Mycobacterium tuberculosis</i>infection in macaques immunized with intravenous BCG" @default.
- W4385685754 doi "https://doi.org/10.4049/jimmunol.210.supp.253.07" @default.
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