Induction of liver-resident memory T cells and protection at liver-stage malaria by mRNA-containing lipid nanoparticles

Recent studies have suggested that CD8(+) liver-resident memory T (T(RM)) cells are crucial in the protection against liver-stage malaria. We used liver-directed mRNA-containing lipid nanoparticles (mRNA-LNPs) to induce liver T(RM) cells in a murine model. Single-dose intravenous injections of ovalbumin mRNA-LNPs effectively induced antigen-specific cytotoxic T lymphocytes in a dose-dependent manner in the liver on day 7. T(RM) cells (CD8(+) CD44(hi) CD62L(lo) CD69(+) KLRG1(-)) were induced 5 weeks after immunization. To examine the protective efficacy, mice were intramuscularly immunized with two doses of circumsporozoite protein mRNA-LNPs at 3-week intervals and challenged with sporozoites of Plasmodium berghei ANKA. Sterile immunity was observed in some of the mice, and the other mice showed a delay in blood-stage development when compared with the control mice. mRNA-LNPs therefore induce memory CD8(+) T cells that can protect against sporozoites during liver-stage malaria and may provide a basis for vaccines against the disease.