Harnessing liver-resident memory T cells for protection against malaria

Abstract

Introduction: Tissue-resident memory T cells (T_RM cells) are powerful mediators of protracted adaptive immunity to infection in peripheral organs. Harnessing T_RM 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 T_RM 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 T_RM cells and discuss the importance of liver T_RM cells in immunity against Plasmodium spp. infection; we summarize current knowledge on T_RM cell biology and discuss the current state and potential of T_RM-based vaccination against malaria.

Expert opinion: T_RM 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 T_RM 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.