TB vaccines; promoting rapid and durable protection in the lung

• Most TB vaccine candidates aim to amplify IFN-γ producing memory T cells in the blood.
• The frequency of IFN-γ producing T cells in blood does not correlate with protection.
• Animal models suggest vaccine-induced T cell responses should be rapid and sustained.
• Lung resident-memory T cells may prevent or curb early infection.
• Central memory T cells migrate to the site of infection and provide durable protection.

TB vaccine discovery has focused on IFN-γ both for the selection of antigens and vaccine delivery strategies. Recent breakthroughs in our understanding of the requirements for immunological memory and the expression of immunity to TB in the lung now provide a framework for reconsidering that strategy. We will discuss the status of the TB vaccine field, recent insights into the role of central memory cells and the potential of tissue-resident memory cells in vaccine promoted protection against TB.