Tuberculosis vaccines - perspectives from the NIH/NIAID Mycobacteria vaccine testing program

Abstract

The development of novel vaccine candidates against infections with Mycobacterium tuberculosis has highlighted our limited understanding of immune mechanisms required to kill M. tuberculosis. The induction of a Th1 immunity is vital, but new studies are required to identify other mechanisms that may be necessary. Novel vaccines formulations that invoke effector cells such as innate lymphoid cells may provide an environment that promote effector mechanisms including T cell and B cell mediated immunity. Identifying pathways associated with killing this highly successful infectious agent has become critical to achieving the goal of reducing the global tuberculosis burden.

Figure 1

The number of protein, recombinant BCG, attenuated M. tuberculosis, DNA/vector and adjuvant formulations submitted for testing by the National Institutes of Health at Colorado State University from 2004 to 2017 in the mouse and guinea pig models of tuberculosis, compared to those currently in clinical trials. The number tested in animal models does not reflect samples tested by individual investigators or at other testing sites.

Figure 2

Designing a novel vaccine against M. tuberculosis infection will require the contribution of a network of cells and signals to promote effective killing mechanisms. Novel vaccine adjuvants stimulate PRR on antigen presenting cells (such as dendritic cells) to augment immunity to antigenic proteins and peptides. The contribution of innate lymphoid cells and non-lymphoid early response cells (e.g. neutrophils), remains to be elucidated. The role of antibody in preventing infection is under extensive investigation, but requires T cell help to ensure the induction of the appropriate antibody.