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ResearchIn-Press PreviewInfectious diseaseVaccines
Open Access | 10.1172/JCI167762
1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Lai, R.
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Gong, D.
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Lindestam Arlehamn, C.
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Acolatse, S.
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Ferris, M.
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Sassetti, C.
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Lauffenburger, D.
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1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Wocester, United States of America
2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States of America
3Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States of America
4Department of Microbiology and Physiological Systems, University of Massachusetts Medical Center, Worcester, United States of America
5Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, San Diego, United States of America
6Texas Biomedical Research Institute, San Antonio, United States of America
7Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States of America
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Behar, S.
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Published May 18, 2023 - More info
Heterogeneity in human immune responses is difficult to model in standard laboratory mice. To understand how host variation affects BCG-induced immunity against Mycobacterium tuberculosis, we studied 24 unique Collaborative Cross (CC) mouse strains, which differ primarily in the genes and alleles they inherit from founder strains. The CC strains were vaccinated with or without BCG, and then challenged with aerosolized M. tuberculosis. As BCG protects only half of the CC strains tested, we conclude that host genetics has a major influence on BCG-induced immunity against M. tuberculosis infection, making it an important barrier to vaccine-mediated protection. Importantly, BCG efficacy is dissociable from inherent susceptibility to TB. T cell immunity was extensively characterized to identify components associated with protection that were stimulated by BCG and recalled after Mtb infection. Although considerable diversity is observed, BCG has little impact on the composition of T cells in the lung after infection. Instead, variability is largely shaped by host genetics. BCG-elicited protection against TB correlated with changes in immune function. Thus, CC mice can be used to define correlates of protection and to identify vaccine strategies that protect a larger fraction of genetically diverse individuals instead of optimizing protection for a single genotype.