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This is further complicated by difficulties in verifying vaccine-induced protection in humans. Although research in animal models, namely mice and nonhuman primates (NHPs), has begun to close this knowledge gap, discrepancies in the relative importance of biological pathways across species limit the utility of animal model\u2013derived biological insights in humans. To address these challenges, we applied a systems modeling framework, Translatable Components Regression (TransCompR), to identify human blood transcriptional variability that could predict\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    challenge outcomes in BCG-vaccinated NHPs. These protection-associated pathways included both innate and adaptive immune activation mechanisms, along with signaling via type I IFNs and antimycobacterial Th cytokines. We further partially validated the associations between these mechanisms and protection in humans using publicly available microarray data collected from BCG-vaccinated infants who either developed TB or remained healthy during 2 years of follow-up. Overall, our work demonstrates how species translation modeling can leverage animal studies to generate hypotheses about the mechanisms that underlie human infectious disease and vaccination outcomes, which may be difficult or impossible to ascertain using human data alone.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.194450","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T17:00:53Z","timestamp":1762880453000},"source":"Crossref","is-referenced-by-count":1,"title":["Cross-species blood transcriptional correlates of BCG-mediated protection against tuberculosis include innate and adaptive immune processes"],"prefix":"10.1172","volume":"10","author":[{"given":"Kate","family":"Bridges","sequence":"first","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Awany","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anele","family":"Gela","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Temwa-Dango","family":"Mwambene","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry L.","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard E.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Elkins","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Sassetti","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1359","authenticated-orcid":true,"given":"Thomas J.","family":"Scriba","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-989X","authenticated-orcid":true,"given":"Douglas A.","family":"Lauffenburger","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"B1","unstructured":"WHO. 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