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.
Competing Interests: SaM is an employee of SHIONOGI & CO., LTD. This work was supported by SHIONOGI & CO., LTD. Osaka, Japan. Nagasaki University and SHIONOGI & CO., LTD. launched the Shionogi Global Infectious Division SHINE at the Institute of Tropical Medicine NEKKEN, Nagasaki University. Based on the contract for this collaboration, SHIONOGI & CO., LTD. provided funding and contributed to improving the work through frequent discussions with the authors. However, SHIONOGI & CO., LTD. had no role in the experiments, data analysis, writing, or reviewing the paper.
(Copyright © 2023 Nakamae, Miyagawa, Ogawa, Kamiya, Taniguchi, Ono, Kawaguchi, Teklemichael, Jian, Araki, Katagami, Mukai, Annoura, Yui, Hirayama, Kawakami and Mizukami.)