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

Taylor W. Foreman, Ashley V. Veatch, Denae N. LoBato, Peter J. Didier, Lara A. Doyle-Meyers, Kasi E. Russell-Lodrigue, Andrew A. Lackner, Konstantin G. Kousoulas, Shabaana A. Khader, Deepak Kaushal, Smriti Mehra

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)2811-2820
Number of pages10
JournalAmerican Journal of Pathology
Volume187
Issue number12
DOIs
StatePublished - Dec 2017

Fingerprint Dive into the research topics of 'Nonpathologic Infection of Macaques by an Attenuated Mycobacterial Vaccine Is Not Reactivated in the Setting of HIV Co-Infection'. Together they form a unique fingerprint.

  • Cite this

    Foreman, T. W., Veatch, A. V., LoBato, D. N., Didier, P. J., Doyle-Meyers, L. A., Russell-Lodrigue, K. E., Lackner, A. A., Kousoulas, K. G., Khader, S. A., Kaushal, D., & Mehra, S. (2017). Nonpathologic Infection of Macaques by an Attenuated Mycobacterial Vaccine Is Not Reactivated in the Setting of HIV Co-Infection. American Journal of Pathology, 187(12), 2811-2820. https://doi.org/10.1016/j.ajpath.2017.08.014