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

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

doi:10.3389/fimmu.2023.1116299

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

Front Immunol. 2023 Aug 23:14:1116299. doi: 10.3389/fimmu.2023.1116299. eCollection 2023.

Authors

Sayuri Nakamae¹, Satoshi Miyagawa^{1

2}, Koki Ogawa³, Mariko Kamiya³, Mayumi Taniguchi¹, Akari Ono³, Maho Kawaguchi³, Awet Alem Teklemichael¹, Jiun-Yu Jian¹, Tamasa Araki⁴, Yukimi Katagami¹, Hidefumi Mukai³, Takeshi Annoura⁴, Katsuyuki Yui⁵, Kenji Hirayama⁶, Shigeru Kawakami³, Shusaku Mizukami^{1

6}

Affiliations

¹ Department of Immune Regulation, Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Nagasaki, Japan.
² Laboratory for Drug Discovery and Disease Research, SHIONOGI & CO., LTD., Osaka, Japan.
³ Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan.
⁴ Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
⁵ Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Nagasaki, Japan.
⁶ School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Nagasaki, Japan.

Abstract

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.

Keywords: cellular immunity; lipid nanoparticles; liver-stage malaria; mRNA; resident memory T cells; vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes*
Liver
Malaria* / prevention & control
Memory T Cells
Mice
RNA, Messenger / genetics
Sporozoites

Substances

Lipid Nanoparticles
RNA, Messenger

Grants and funding

SN received financial support from Center for Diversity and Inclusion, Nagasaki university for English editing. their discussions on setting up our experimental systems with lipid nanoparticles; and Mr. Tomonari Masuda and Mr. Makoto Matsumoto for their preparation of lipid nanoparticles. This study was conducted (in part) at the Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Japan.