Host genetic background is a barrier to broadly effective vaccine–mediated protection against tuberculosis
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Le résumé fourni par la source
Heterogeneity in human immune responses is difficult to model in standard laboratory mice. To understand how host variation affects Bacillus Calmette Guerin-induced (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 challenged with aerosolized M. tuberculosis. Since BCG protects only half of the CC strains tested, we concluded 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 tuberculosis (TB). T cell immunity was extensively characterized to identify components associated with protection that were stimulated by BCG and recalled after M. tuberculosis 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.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Host genetic background is a barrier to broadly effective vaccine–mediated protection against tuberculosis
- Date Crossref
- 03/07/2023
- Éditeur
- American Society for Clinical Investigation
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Massachusetts Chan Medical School pays non établi dans la noticeUniversité ou école supérieure
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Massachusetts Institute of Technology Department of Biological Engineering pays non établi dans la noticeUniversité ou école supérieure
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La Jolla Institute for Immunology Center for infectious disease and vaccine research pays non établi dans la noticeOrganisation à but non lucratif
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Texas Biomedical Research Institute pays non établi dans la noticeStructure de recherche
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University of North Carolina at Chapel Hill Department of Genetics pays non établi dans la noticeUniversité ou école supérieure
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University of Massachusetts Medical School Department of Microbiology and Physiological Systems pays non établi dans la noticeUniversité ou école supérieure
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University of Massachusetts Medical Center Department of Microbiology and Physiological Systems pays non établi dans la noticeUniversité ou école supérieure
University of Massachusetts Chan Medical School, Department of Biological Engineering — Massachusetts Institute of Technology et Center for infectious disease and vaccine research — La Jolla Institute for Immunology, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.