Intravenous Bacille Calmette-Guérin vaccination protects simian immunodeficiency virus-infected macaques from tuberculosis

静脉注射卡介苗可保护感染猴免疫缺陷病毒的猕猴免受结核病侵害

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作者: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

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the most common cause of death in people living with human immunodeficiency virus (HIV). Intra-dermal Bacille Calmette-Guérin (BCG) delivery is the only licensed vaccine against tuberculosis; however, it offers little protection from pulmonary tuberculosis in adults and is contraindicated in people living with HIV. Intravenous BCG confers protection against Mtb infection in rhesus macaques; we hypothesized that it might prevent tuberculosis in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. Here intravenous BCG-elicited robust airway T cell influx and elevated plasma and airway antibody titres in both SIV-infected and naive animals. Following Mtb challenge, all 7 vaccinated SIV-naive and 9 out of 12 vaccinated SIV-infected animals were protected, without any culturable bacteria detected from tissues. Peripheral blood mononuclear cell responses post-challenge indicated early clearance of Mtb in vaccinated animals, regardless of SIV infection. These data support that intravenous BCG is immunogenic and efficacious in SIV-infected animals.

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