Intravenous BCG induces a more potent airway and lung immune response than intradermal BCG in SIV-infected macaques.

Autor: Jauro S; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Larson EC; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Gleim JL; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Wahlberg BM; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Rodgers MA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Chehab JC; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Lopez-Velazques AE; Department of Biology, University of Puerto Rico - Humacao Campus, Puerto Rico, USA., Ameel CL; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Tomko JA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Sakal JL; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., DeMarco T; Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Borish HJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Maiello P; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Potter EL; Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA., Roederer M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA., Lin PL; Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.; Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Flynn JL; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Scanga CA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 22. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1101/2024.07.17.603921
Abstrakt: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates Mtb infection outcomes in people living with HIV (PLWH). Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. Here, we investigated the immune responses elicited by BCG administered via intravenous (IV) or intradermal (ID) routes in Simian Immunodeficiency Virus (SIV)-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of Mtb challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic molecules, and key transcription factors. Our results showed that IV BCG induces a robust and sustained immune response, including tissue-resident memory T (T RM ) cells in lungs, polyfunctional CD4+ and CD8αβ+ T cells expressing multiple cytokines, and CD8αβ+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of IV BCG-vaccinated MCM. Although IV BCG vaccination resulted in an influx of T RM cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>10 5 copies/mL) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on IV BCG-induced protection against Mtb.
Databáze: MEDLINE