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Nonpathologic Infection of Macaques by an Attenuated Mycobacterial Vaccine Is Not Reactivated in the Setting of HIV Co-Infection.

Authors
  • Foreman, Taylor W1
  • Veatch, Ashley V2
  • LoBato, Denae N2
  • Didier, Peter J2
  • Doyle-Meyers, Lara A2
  • Russell-Lodrigue, Kasi E2
  • Lackner, Andrew A1
  • Kousoulas, Konstantin G3
  • Khader, Shabaana A4
  • Kaushal, Deepak5
  • Mehra, Smriti6
  • 1 Tulane National Primate Research Center, Covington, Louisiana; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana.
  • 2 Tulane National Primate Research Center, Covington, Louisiana.
  • 3 Center for Biomedical Research Excellence, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana; Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana.
  • 4 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
  • 5 Tulane National Primate Research Center, Covington, Louisiana; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address: [email protected]
  • 6 Tulane National Primate Research Center, Covington, Louisiana; Center for Biomedical Research Excellence, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana; Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana. Electronic address: [email protected]
Type
Published Article
Journal
American Journal Of Pathology
Publisher
Elsevier
Publication Date
Dec 01, 2017
Volume
187
Issue
12
Pages
2811–2820
Identifiers
DOI: 10.1016/j.ajpath.2017.08.014
PMID: 28935575
Source
Medline
License
Unknown

Abstract

Failure to replace Bacille Calmette-Guerin vaccines with efficacious anti-tuberculosis (TB) vaccines have prompted outside-the-box thinking, including pulmonary vaccination to elicit local immunity. Inhalational MtbΔsigH, a stress-response-attenuated strain, protected against lethal TB in macaques. While live mycobacterial vaccines show promising efficacy, HIV co-infection and the resulting immunodeficiency prompts safety concerns about their use. We assessed the persistence and safety of MtbΔsigH, delivered directly to the lungs, in the setting of HIV co-infection. Macaques were aerosol-vaccinated with ΔsigH and subsequently challenged with SIVmac239. Bronchoalveolar lavage and tissues were sampled for mycobacterial persistence, pathology, and immune correlates. Only 35% and 3.5% of lung samples were positive for live bacilli and granulomas, respectively. Our results therefore suggest that the nonpathologic infection of macaque lungs by ΔsigH was not reactivated by simian immunodeficiency virus, despite high viral levels and massive ablation of pulmonary CD4+ T cells. Protective pulmonary responses were retained, including vaccine-induced bronchus-associated lymphoid tissue and CD8+ effector memory T cells. Despite acute simian immunodeficiency virus infection, all animals remained asymptomatic of pulmonary TB. These findings highlight the efficacy of mucosal vaccination via this attenuated strain and will guide its further development to potentially combat TB in HIV-endemic areas. Our results also suggest that a lack of pulmonary pathology is a key correlate of the safety of live mycobacterial vaccines.

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