{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T02:33:47Z","timestamp":1768530827453,"version":"3.49.0"},"posted":{"date-parts":[[2025,10,30]]},"group-title":"Immunology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["P01 AI123286"],"award-info":[{"award-number":["P01 AI123286"]}]},{"name":"NIH","award":["R01 AI172905"],"award-info":[{"award-number":["R01 AI172905"]}]},{"name":"NIH","award":["R01 HL145411"],"award-info":[{"award-number":["R01 HL145411"]}]},{"name":"NIH","award":["Contract No. 75N93019C00071"],"award-info":[{"award-number":["Contract No. 75N93019C00071"]}]},{"name":"NIH","award":["T32 AI007349"],"award-info":[{"award-number":["T32 AI007349"]}]},{"name":"NIH","award":["T32 GM159591"],"award-info":[{"award-number":["T32 GM159591"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract\/Summary<\/jats:title>\n                <jats:p>\n                  Vaccine development for tuberculosis is a global priority. Our studies using Collaborative Cross (CC) mice show that genetic diversity influences the efficacy of BCG, the most widely used TB vaccine. BCG vaccination of CC042 mice reduces their lung bacillary burden and increases their survival following low-dose aerosol\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  infection (MTBI), despite impaired T cell trafficking from a defective\n                  <jats:italic>Itgal<\/jats:italic>\n                  gene. Early protection requires the presence of T cells at the time of BCG vaccination but is not mediated by B cell or T cell recall responses following MTBI. In contrast, T cell depletion following BCG vaccination reduces survival after MTBI. Thus, CC042 mice reveal two phases of immunity induced by BCG that require T cells: an early phase mediated by innate responses and a later phase mediated by effector CD4 and\/or CD8 T cells. Although measurement of vaccine-induced protection 30 days after MTBI is a standard measure of vaccine efficacy in the murine TB model, we find this time point is independent of memory T cells. Our results suggest that vaccine-elicited innate responses have a larger role in protection than previously considered. The concordance between lung CFU, pathology, and survival make CC042 mice a useful model for vaccine evaluation.\n                <\/jats:p>","DOI":"10.1101\/2025.10.28.685186","type":"posted-content","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T21:05:46Z","timestamp":1761858346000},"source":"Crossref","is-referenced-by-count":0,"title":["BCG vaccination elicits protection against Mtb infection mediated by two phases of T cell immunity"],"prefix":"10.64898","author":[{"given":"Abiola F.","family":"Ogunsola","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocky","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Cavallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian L.","family":"Beamer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-6699","authenticated-orcid":false,"given":"Samuel M.","family":"Behar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025110308450654000_2025.10.28.685186v1.1","unstructured":"World Health O. 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Host genetic background is a barrier to broadly effective vaccine\u2013mediated protection against tuberculosis. The Journal of Clinical Investigation. 2024;133(13).","DOI":"10.1172\/JCI167762"},{"key":"2025110308450654000_2025.10.28.685186v1.11","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.132639"},{"key":"2025110308450654000_2025.10.28.685186v1.12","doi-asserted-by":"crossref","unstructured":"Smith CM , Proulx MK , Olive AJ , Laddy D , Mishra BB , Moss C , et al. Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype. mBio. 2016;7(5).","DOI":"10.1128\/mBio.01516-16"},{"key":"2025110308450654000_2025.10.28.685186v1.13","unstructured":"Smith CM , Baker RE , Proulx MK , Mishra BB , Long JE , Park SW , et al. Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice. 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