Intravenous Bacille Calmette-Guerin provides protection across a dose spectrum in a Rhesus macaque model of tuberculosis

• DOI: 10.4049/jimmunol.202.supp.139.3
• Publication Date: 2023-01-02T03:20:43Z
• Authors: Joseph John Zeppa; Patricia A Darrah; Supriya Pokkali; Joshua A Hackney; Pauline A Maiello; Charles A Scanga; Dominick J Laddy; Philiana Ling Lin; Robert A Seder; Mario Roederer; JoAnne L Flynn
• Keywords: Rhesus macaque

Abstract Our laboratory has demonstrated that intravenous (IV) vaccination with Bacille Calmette-Guerin (BCG; 5x107CFU) provides remarkably robust protection against low-dose Mycobacterium tuberculosis (Mtb) infection in Rhesus macaques (9/10 animals protected [<50 thoracic Mtb CFU]; 100,000-fold reduction compared to intradermal [ID] BCG). IV BCG also resulted a 100-fold increase mycobacterium-specific T cells the bronchoalveolar lavage (BAL) of other routes administration (ID or aerosol). These results led us hypothesize significant could be observed at lower doses. We therefore vaccinated decreasing doses (5x107, 1.6x107, 5x106, 1.6x106, 5x105and 1.6 x105CFU) followed by six months immune monitoring and three-month challenge. As expected, cell dose-dependent response was both BAL (FACS) PBMCs (IFNgELIspot) prior infection, as well lung time necropsy (FACS). Remarkably, 17/25 had no CFU across all groups, least one animal from each group (30–100% protection). Mycobacterium-specific CD4 numbers appear correlate protection. demonstrate even low can efficacious preventing potential role for cell-dependent immunity.