Introduction: Tissue-resident memory T cells (TRM cells) are powerful mediators of protracted adaptive immunity to infection in peripheral organs. Harnessing TRM cells through vaccination hence promises unprecedented potential for protection against infection. A paramount example of this is malaria, a major infectious disease for which immunity through traditional vaccination strategies remains challenging. Liver TRM cells appear to be highly protective against malaria, and recent developments in our knowledge of the biology of these cells have defined promising, novel strategies for their induction.
Areas covered: Here, we describe the path that led to the discovery of TRM cells and discuss the importance of liver TRM cells in immunity against Plasmodium spp. infection; we summarize current knowledge on TRM cell biology and discuss the current state and potential of TRM-based vaccination against malaria.
Expert opinion: TRM based vaccination has emerged as a promising means to achieve efficient protection against malaria. Recent advances provide a solid basis for continuing the development of this area of research. Deeper understanding of the mechanisms that mediate TRM formation and maintenance and identification of immunogenic and protective target epitopes suitable for human vaccination remain the main challenges for translation of these discoveries.
Keywords: CD8+ T cells; RTS; S; T cell memory; T cell-based vaccination; Tissue-resident memory T cells; liver immunology; malaria; pre-erythrocytic stages of Plasmodium; prime-and-trap; whole sporozoite malaria vaccines.