Dendritic Cell Vaccine Harboring Inactivated Mycobacteria Induces Immune Protection Against Tuberculosis in Murine Models and is Well Tolerated in Humans.

Abstract

The limited success of tuberculosis (TB) control measures reflects the inadequacy of Bacille Calmette-Guérin (BCG), the only licensed TB vaccine. There is a recent resurgence of interest in intravenous administration of BCG. However, direct injection of live BCG bacteria into the bloodstream of human beings is not likely to be practical due to safety concerns. In this study, it is showed that debris of BCG-infected macrophages induces activation and maturation of dendritic cells (DCs) in vitro, and an intravenous DCs vaccine phagocytosing noninfective cell debris induces robust antigen-specific T-cell immune responses and immune protection against Mycobacterium tuberculosis infection in murine models. Further, an investigator-initiated clinical trial shows the safety of a DCs vaccine harboring the noninfective Mycobacterium vaccae vaccine. Infusions of naive DCs and DCs harboring Mycobacterium vaccae are well tolerated and safe in six active TB patients. Tests of the peripheral blood mononuclear cells of a patient who receives two doses of DCs vaccine infusion show enhanced secretion of IFN-γ, IL-2, IL-17, and TNF-α in both CD4 and CD8 T cells. The study provides evidence that DC-based vaccines harboring inactivated mycobacteria can expand T-cell immune responses in TB-infected mice and are well tolerated in patients with active TB disease.