Repetitive vaccination with intravenous BCG is safe and immunogenic in naïve and SIV-infected macaques

Abstract Tuberculosis (TB) is the leading cause of death in people with HIV (PWH) on or off antiretroviral therapy (ART); thus, new TB vaccine candidates should be evaluated setting HIV. Mycobacterium bovis Bacillus Calmette-Guerin (BCG), live attenuated bacterial given intradermally (ID) at birth, contraindicated PWH. We recently demonstrated that intravenous (IV) delivery BCG elicits superior immunity and protection compared to ID against tuberculosis (Mtb) challenge rhesus macaques. To assess IV an animal model infection, we immunized SIVmac251-infected macaques suppresive ART (6m) uninfected controls. Rhesus received three doses BCG, 8wks apart, were monitored for presence colony forming units (CFU) peripheral blood bronchoalveolar lavage (BAL) Mtb-specific T cell responses BAL. Repetitive immunization was well-tolerated SIV-infected animals, no difference clinical parameters CFU after similar, both groups displaying a 10–50 fold increase BAL abundance initial dose. CD4 CD8 peaked dose maintained by subsequent immunizations least 6m. These data indicate safe immunogenic SIV-infected, ART-suppressed boosting maintains site infection. NIH Intramural Program