Vaccination with intravenous BCG protects macaques with pre-existing SIV infection from tuberculosis.

Autor:	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., Ellis-Connell AL; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, USA., Rodgers MA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Gubernat AK; Department of Microbiology and Molecular Genetics, 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., Moriarty RV; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, USA., Balgeman AJ; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, USA., Ameel CL; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Jauro S; 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., Kracinovsky KB; 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., Borish HJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., White AG; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Klein E; Division of Laboratory Animal Resources, School of Medicine, University of Pittsburgh, PA, USA., Bucsan AN; Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA., Darrah PA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA., Seder RA; 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; 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., O'Connor SL; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, USA.; Wisconsin National Primate Research Center, University of Wisconsin - Madison, Madison, WI, 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:	Research square [Res Sq] 2023 Apr 17. Date of Electronic Publication: 2023 Apr 17.
DOI:	10.21203/rs.3.rs-2802306/v1
Abstrakt:	Tuberculosis (TB) is the most common cause of death in people living with HIV. BCG delivered intradermally (ID) is the only licensed vaccine to prevent TB. However, it offers little protection from pulmonary TB in adults. Intravenous (IV) BCG, but not ID BCG, confers striking protection against Mycobacterium tuberculosis (Mtb) infection and disease in rhesus macaques. We investigated whether IV BCG could protect against TB in macaques with a pre-existing SIV infection. There was a robust influx of airway T cells following IV BCG in both SIV-infected and SIV-naïve animals, with elevated antibody titers in plasma and airways. Following Mtb challenge, all 7 SIV-naïve and 9 out of 12 SIV-infected vaccinated animals were completely protected, without any culturable bacilli in their tissues. PBMC responses post-challenge indicated early clearance of Mtb in vaccinated animals regardless of SIV infection. These data support that IV BCG is immunogenic and efficacious in SIV-infected animals. Competing Interests: Ethics statement No authors at the University of Pittsburgh, University of Wisconsin-Madison, and NIH have competing interests.
Databáze:	MEDLINE
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