Evaluation of the time needed for BCG to be alive to protect against tuberculosis in intravenously BCG vaccinated SIV+ macaques.

Abstract Effective means of improving Bacille Calmette-Guérin (BCG) immunogenicity to protect against pulmonary tuberculosis (TB) is needed, especially among people living with HIV. Intravenous (IV) administration BCG previously showed significant enhancement immune responses and conferred ~75% protection TB. Using our SIV/M. (Mtb) coinfection model (to mimic HIV/Mtb coinfection) in Mauritius cynomolgus macaques (MCM), we evaluated the length time necessary for live elicit a protective by varying timing anti-BCG drug (isoniazid, rifampicin, ethambutol: HRE) initiation. MCM were infected SIVmac239 randomly assigned into 4 different vaccination groups 16 weeks after SIV infection: intradermal (BCG ID No HRE), IV HRE started 1 week post 1wk 3 3wks without treatment HRE). The lasted 8 weeks. Airways samples collected bronchoalveolar lavage (BAL), whereas lung tissue lymph node harvested at necropsy subset vaccinated 20 but before challenge. remaining challenged Mtb Erdman strain (~15 CFU). CD4 CD8 T cell levels increased BAL all MCM. cells producing IFNg, IL-2, IL-17, TNF peaked maintained until necropsy. There tissue-resident cytokine production lungs compared ID. signs dissemination apparent any We are currently evaluating infection disease SIV+ each group. Supported grant NIH (R01 AI155345)