Immunogenicity of intravenous irradiated or auxotrophic BCG immunization in macaques

Abstract Tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis (Mtb), is a leading cause of death worldwide, particularly in people with HIV. The current vaccine against TB, BCG, is a live-attenuated strain of M. bovis that is administered intradermally at birth in endemic countries. BCG protects children against disseminated TB but fails to protect adolescents and adults against pulmonary TB, the most transmissible form. Thus, more effective TB vaccines are urgently needed. We previously demonstrated that delivering BCG intravenously (IV) elicits a high number of Mtb-specific T cells in the airway, the site of infection, and confers robust protection against Mtb challenge 6 months later in rhesus macaques. While whole organism vaccines provide broad antigenic breadth, safety concerns may limit clinical development of a replication-competent IV BCG regimen, especially in immunocompromised individuals. To address this, we vaccinated macaques IV with either irradiation-inactivated (Ird) BCG or a live, replication-incompetent auxotroph (Aux) of BCG and compared their immunogenicity in the bronchoalveolar lavage (BAL) to wild type (WT) BCG. Early results indicate that Aux BCG elicits a similar magnitude of Mtb-specific T cell responses in the BAL compared to WT BCG; in contrast, Ird BCG is less potent in generating such responses. These studies provide data on whether whole organism vaccines need to be live, persist, or replicate to confer durable immunity against TB. Funded by the NIH Intramural Program