Table 1.

The TB Immunogram

Challenge	Strategies
Different vaccine approaches needed for distinct populations	Optimize animal models to test vaccines for naive, BCG-vaccinated, LTBI, and active TB.
Optimal vaccine antigens not known	Consider different antigens for distinct target populations.Examine antigen properties beyond frequency or magnitude of T cell responses.Prioritize antigens presented by HLA alleles prevalent in regions with high TB burdens.
Vaccine-induced T cells require a combination of properties	Assay vaccines for induction of T cells with appropriate state of differentiation, residence in lung tissue compartments, and expression of effector mechanisms beyond cytokine secretion.
M. tuberculosis-infected cells evade T cell recognition	Identify antigens less impacted by evasion mechanisms (nonsecreted antigens, antigens with evidence of selection pressure from T cell recognition); develop pharmacological interventions to overcome specific evasion mechanisms. Exploit trained innate immunity for T cell-independent protection.
M. tuberculosis occupies diverse intracellular compartments	Identify mechanisms for elimination of bacteria in immature phagosomes, cytoplasm, autophagosomes, and mature phagolysosomes.
M. tuberculosis can be extracellular	Determine the bacterial population fraction that is extracellular during distinct stages of infection; optimize antibodies and other humoral mediators.
Range of inoculum size unknown in humans	Examine vaccines efficacious against low-dose challenges for efficacy against higher inocula and more virulent bacterial strains.
Correlates of immunity not identified	Develop methods for analysis of cells in human tissues; apply analyses that account for nonlinear relationships between response and protection.