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

2023; Frontiers Media; Volume: 14; Linguagem: Inglês

10.3389/fimmu.2023.1116299

1664-3224

Sayuri Nakamae, Satoshi Miyagawa, Koki Ogawa, Mariko Kamiya, Mayumi Taniguchi, Akari Ono, Maho Kawaguchi, Awet Alem Teklemichael, Jiun‐Yu Jian, Tamasa Araki, Yukimi Katagami, Hidefumi Mukai, Takeshi Annoura, Katsuyuki Yui, Kenji Hirayama, Shigeru Kawakami, Shusaku Mizukami,

Complement system in diseases

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.