Frontiers in Immunology (Aug 2023)

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

  • Sayuri Nakamae,
  • Satoshi Miyagawa,
  • 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,
  • Shusaku Mizukami

DOI
https://doi.org/10.3389/fimmu.2023.1116299
Journal volume & issue
Vol. 14

Abstract

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Recent studies have suggested that CD8+ liver-resident memory T (TRM) cells are crucial in the protection against liver-stage malaria. We used liver-directed mRNA-containing lipid nanoparticles (mRNA-LNPs) to induce liver TRM 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. TRM cells (CD8+ CD44hi CD62Llo 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.

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