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

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1116299

DOI=10.3389/fimmu.2023.1116299

ISSN=1664-3224

ABSTRACT=<p>Recent studies have suggested that CD8<sup>+</sup> liver-resident memory T (T<sub>RM</sub>) cells are crucial in the protection against liver-stage malaria. We used liver-directed mRNA-containing lipid nanoparticles (mRNA-LNPs) to induce liver T<sub>RM</sub> 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<sub>RM</sub> cells (CD8<sup>+</sup> CD44<sup>hi</sup> CD62L<sup>lo</sup> CD69<sup>+</sup> KLRG1<sup>-</sup>) 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 <italic>Plasmodium berghei</italic> 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<sup>+</sup> T cells that can protect against sporozoites during liver-stage malaria and may provide a basis for vaccines against the disease.</p>