澳大利亚墨尔本大学William R. Heath、新西兰莫里斯·威尔金斯分子生物发现中心Ian F. Hermans和Gavin F. Painter小组，合作报道了特异性靶向肝脏驻留记忆T细胞（Trm细胞）的疟疾mRNA疫苗。2023年7月20日出版的《自然—免疫学》杂志发表了这项成果。

最近的研究证明肝脏组织驻留记忆T细胞可以控制疟疾在肝脏期的感染，研究人员采取了基于信使RNA（mRNA）的疫苗来诱导肝脏Trm细胞以预防疟疾。尽管标准mRNA疫苗无法在小鼠中产生肝脏Trm或防止Plasmodium berghei孢子体的攻击，但在mRNA疫苗接种后通过添加由I型自然杀伤T细胞产生的激动剂可招募T细胞，这会诱导肝脏Trm细胞的显著增加并产生有效的保护。

此外，虽然小鼠先前暴露于血期感染损害了基于减毒孢子体的传统疫苗，但mRNA疫苗接种人群不受影响，这突显了在疟疾流行地区采取这种合理的基于mRNA疫苗策略的潜力。

据介绍，疟疾是由按蚊传播的疟原虫引起。蚊虫叮咬后，疟原虫孢子体从皮肤迁移到肝脏，在那里发生广泛复制，随后以裂殖子的形式出现，可以感染红细胞并引发疾病症状。

附：英文原文

Title: mRNA vaccine against malaria tailored for liver-resident memory T cells

Author: Ganley, Mitch, Holz, Lauren E., Minnell, Jordan J., de Menezes, Maria N., Burn, Olivia K., Poa, Kean Chan Yew, Draper, Sarah L., English, Kieran, Chan, Susanna T. S., Anderson, Regan J., Compton, Benjamin J., Marshall, Andrew J., Cozijnsen, Anton, Chua, Yu Cheng, Ge, Zhengyu, Farrand, Kathryn J., Mamum, John C., Xu, Calvin, Cockburn, Ian A., Yui, Katsuyuki, Bertolino, Patrick, Gras, Stephanie, Le Nours, Jrme, Rossjohn, Jamie, Fernandez-Ruiz, Daniel, McFadden, Geoffrey I., Ackerley, David F., Painter, Gavin F., Hermans, Ian F., Heath, William R.

Issue&Volume: 2023-07-20

Abstract: Malaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked on a messenger RNA (mRNA)-based vaccine strategy to induce liver Trm cells to prevent malaria. Although a standard mRNA vaccine was unable to generate liver Trm or protect against challenge with Plasmodium berghei sporozoites in mice, addition of an agonist that recruits T cell help from type I natural killer T cells under mRNA-vaccination conditions resulted in significant generation of liver Trm cells and effective protection. Moreover, whereas previous exposure of mice to blood-stage infection impaired traditional vaccines based on attenuated sporozoites, mRNA vaccination was unaffected, underlining the potential for such a rational mRNA-based strategy in malaria-endemic regions.

DOI: 10.1038/s41590-023-01562-6

Source: https://www.nature.com/articles/s41590-023-01562-6