Protecting simian immunodeficiency virus-infected macaques from Mycobacterium tuberculosis by intravenous Bacillus Calmette-Guérin vaccination requires viral control 2308

Abstract Description Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global health challenge, especially for people living with HIV (PLWH) not on antiretroviral therapy (ART). We previously showed that intravenous Bacillus Calmette-Guérin (IV BCG) provides robust protection in SIV+ macaques. This study evaluated the immunogenicity and protective efficacy of IV BCG in SIV+ macaques treated for 8 weeks with an anti-BCG regimen of isoniazid, rifampicin, and ethambutol (HRE), starting either 1 week (early) or 3 weeks (late) post-BCG. Control groups included IV BCG-vaccinated macaques without HRE and those vaccinated with intradermal (ID) BCG. Five months post-vaccination, macaques were challenged with Mtb, and TB progression was monitored by PET-CT imaging and bacterial load at necropsy 12 weeks post-challenge. IV BCG induced stronger immune responses than ID BCG. Protection conferred by IV BCG was significant regardless of HRE timing. However, SIV non-controllers, marked by high viremia and reduced CD4+ T cells in the lungs, showed less protection than SIV controllers. This study confirms the robust efficacy of IV BCG in SIV+ macaques, even with short BCG exposure times. It further demonstrates the critical importance of viral control in vaccine-elicited protection from TB in PLWH. Funding Sources Funding: NIH R01AI155345 (Scanga); NIH Contract HHSN272201800003C (Demarco) Topic Categories Vaccines and Immunotherapy (VAC)