Table 3.

Scientific gaps and opportunities in TB research.

Immunology Evaluate in depth, innate and adaptive immune responses to Mtb in the lung (including role of resident memory T cells) Determine the role of B cells and functional Abs during Mtb infection and delineate their functions Assess role of unconventional T cell types in Mtb infection and following vaccination Expand type and combinations of Ags to be included in TB vaccine candidates and develop a better understanding of the effect of quality versus quantity in Ag selection, choice of adjuvant and delivery systems. Determine Ags recognized in the lung at different stages of Mtb infection Evaluate potential role of microbiome in Mtb- or TB vaccine- induced immunity and TB disease progression Assess role of trained immunity and whether it could be harnessed for TB vaccine development

Model/assay development Improve animal models to better mirror human Mtb infection and kinetics of development of TB disease, for use in both basic and pre-clinical research including vaccine candidate selection Develop microbial readout assays to measure bacillary burden during disease progression and following treatment

Human studies Study the dynamics of Mtb vaccine-induced responses in humans of various age groups to understand how they differ in pre- and post-exposure vaccination and in the presence of immune modulating co-morbidities (e.g. diabetes) Design human experimental vaccines studies to answer critical immunological questions in addition to continue evaluating vaccine candidates with a defined clinical path Comprehensively survey entire immune space during Mtb infection and TB disease akin to efforts that have been made in the HIV field