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ResearchIn-Press PreviewImmunologyInfectious diseaseInflammation Open Access | 10.1172/jci.insight.201000

BCG vaccination elicits protection against Mtb infection mediated by two phases of T cell immunity

Abiola F. Ogunsola,1 Rocky Lai,2 Kelly Cavallo,2 Anthony V. Tran,4 Gillian L. Beamer,5 and Samuel M. Behar1

1MD/PhD Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, United States of America

2Department of Microbiology, University of Massachusetts Chan Medical School, Wocester, United States of America

3Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, United States of America

4Medical Scientist Training Program, University of Massachusetts Chan Medical School, Worcester, United States of America

5Texas Biomedical Research Institute, San Antonio, United States of America

Find articles by Ogunsola, A. in: PubMed | Google Scholar

1MD/PhD Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, United States of America

2Department of Microbiology, University of Massachusetts Chan Medical School, Wocester, United States of America

3Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, United States of America

4Medical Scientist Training Program, University of Massachusetts Chan Medical School, Worcester, United States of America

5Texas Biomedical Research Institute, San Antonio, United States of America

Find articles by Lai, R. in: PubMed | Google Scholar |

1MD/PhD Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, United States of America

2Department of Microbiology, University of Massachusetts Chan Medical School, Wocester, United States of America

3Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, United States of America

4Medical Scientist Training Program, University of Massachusetts Chan Medical School, Worcester, United States of America

5Texas Biomedical Research Institute, San Antonio, United States of America

Find articles by Cavallo, K. in: PubMed | Google Scholar

1MD/PhD Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, United States of America

2Department of Microbiology, University of Massachusetts Chan Medical School, Wocester, United States of America

3Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, United States of America

4Medical Scientist Training Program, University of Massachusetts Chan Medical School, Worcester, United States of America

5Texas Biomedical Research Institute, San Antonio, United States of America

Find articles by Tran, A. in: PubMed | Google Scholar

1MD/PhD Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, United States of America

2Department of Microbiology, University of Massachusetts Chan Medical School, Wocester, United States of America

3Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, United States of America

4Medical Scientist Training Program, University of Massachusetts Chan Medical School, Worcester, United States of America

5Texas Biomedical Research Institute, San Antonio, United States of America

Find articles by Beamer, G. in: PubMed | Google Scholar

1MD/PhD Program, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, United States of America

2Department of Microbiology, University of Massachusetts Chan Medical School, Wocester, United States of America

3Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, United States of America

4Medical Scientist Training Program, University of Massachusetts Chan Medical School, Worcester, United States of America

5Texas Biomedical Research Institute, San Antonio, United States of America

Find articles by Behar, S. in: PubMed | Google Scholar |

Published July 2, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.201000.
Copyright © 2026, Ogunsola et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 2, 2026 - Version history
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Abstract

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 reduced their lung bacillary burden and increased their survival following low-dose aerosol Mycobacterium tuberculosis infection (MTBI), despite impaired T cell trafficking due to a defective Itgal gene. BCG vaccination conferred early bacillary control which appeared to be independent of B cell or T cell recall responses following MTBI. In contrast, long term survival of BCG-vaccinated CC042 mice after MTBI required T cells. Thus, CC042 mice reveal two phases of immunity induced by BCG: an early phase mediated by innate immunity or innate-like T cells and a later phase mediated by conventional memory 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 TB model, this time point might be independent of memory T cells in CC042 mice. Our results suggest that vaccine-elicited innate/innate-like responses could have a larger role in protection than previously considered. The concordance between lung CFU, pathology, and survival make CC042 mice useful for mechanistic studies on vaccine-induced immunity.

Graphical Abstract
graphical abstract
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View Table of antibodies used in study.

Version history
  • Version 1 (July 2, 2026): In-Press Preview
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