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

Erica C Larson; Amy L Ellis-Connell; Mark A Rodgers; Abigail K Gubernat; Janelle L Gleim; Ryan V Moriarty; Alexis J Balgeman; Cassaundra L Ameel; Solomon Jauro; Jaime A Tomko; Kara B Kracinovsky; Pauline Maiello; H Jake Borish; Alexander G White; Edwin Klein; Allison N Bucsan; Patricia A Darrah; Robert A Seder; Mario Roederer; Philana Ling Lin; JoAnne L Flynn; Shelby L O'Connor; Charles A Scanga

doi:10.21203/rs.3.rs-2802306/v1

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

Res Sq [Preprint]. 2023 Apr 17:rs.3.rs-2802306. doi: 10.21203/rs.3.rs-2802306/v1.

Authors

Erica C Larson^{1

2}, Amy L Ellis-Connell³, Mark A Rodgers¹, Abigail K Gubernat¹, Janelle L Gleim¹, Ryan V Moriarty³, Alexis J Balgeman³, Cassaundra L Ameel¹, Solomon Jauro¹, Jaime A Tomko¹, Kara B Kracinovsky¹, Pauline Maiello¹, H Jake Borish¹, Alexander G White¹, Edwin Klein⁴, Allison N Bucsan⁵, Patricia A Darrah⁵, Robert A Seder⁵, Mario Roederer⁵, Philana Ling Lin⁶, JoAnne L Flynn^{1

2}, Shelby L O'Connor^{3

7}, Charles A Scanga^{1

2}

Affiliations

¹ Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
² Center for Vaccine Research, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
³ Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Madison, WI, USA.
⁴ Division of Laboratory Animal Resources, School of Medicine, University of Pittsburgh, PA, USA.
⁵ Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
⁶ Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
⁷ Wisconsin National Primate Research Center, University of Wisconsin - Madison, Madison, WI, USA.

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.

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Preprint

Abstract

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