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Vaccination with intravenous BCG protects macaques with pre-existing SIV infection from tuberculosis.
Larson, Erica C; Ellis-Connell, Amy L; Rodgers, Mark A; Gubernat, Abigail K; Gleim, Janelle L; Moriarty, Ryan V; Balgeman, Alexis J; Ameel, Cassaundra L; Jauro, Solomon; Tomko, Jaime A; Kracinovsky, Kara B; Maiello, Pauline; Borish, H Jake; White, Alexander G; Klein, Edwin; Bucsan, Allison N; Darrah, Patricia A; Seder, Robert A; Roederer, Mario; Lin, Philana Ling; Flynn, JoAnne L; O'Connor, Shelby L; Scanga, Charles A.
Affiliation
  • Larson EC; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  • Ellis-Connell AL; Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  • Rodgers MA; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, 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 Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  • Balgeman AJ; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, USA.
  • Ameel CL; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, 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; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  • Bucsan AN; Division of Laboratory Animal Resources, School of Medicine, University of Pittsburgh, PA, 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; Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Flynn JL; Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  • O'Connor SL; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  • Scanga CA; Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
Res Sq ; 2023 Apr 17.
Article in En | MEDLINE | ID: mdl-37090620
ABSTRACT
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.

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Res Sq Year: 2023 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Res Sq Year: 2023 Document type: Article Affiliation country: