Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital of Bonn, Bonn, NRW, 53127, Germany.
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Cell Host Microbe. 2020 Jun 10;27(6):950-962.e7. doi: 10.1016/j.chom.2020.04.010. Epub 2020 May 11.
Liver-resident memory CD8 T (T) cells remain in and constantly patrol the liver to elicit rapid immunity upon antigen encounter and can mediate efficient protection against liver-stage Plasmodium infection. This finding has prompted the development of immunization strategies where T cells are activated in the spleen and then trapped in the liver to form T cells. Here, we identify PbRPL6, a H2-K-restricted epitope from the putative 60S ribosomal protein L6 (RPL6) of Plasmodium berghei ANKA, as an optimal antigen for endogenous liver T cell generation and protection against malaria. A single dose vaccination targeting RPL6 provided effective and prolonged sterilizing immunity against high dose sporozoite challenges. Expressed throughout the parasite life cycle, across Plasmodium species, and highly conserved, RPL6 exhibits strong translation potential as a vaccine candidate. This is further advocated by the identification of a broadly conserved, immunogenic HLA-A02:01-restricted epitope in P. falciparum RPL6.
肝驻留记忆 CD8 T（T）细胞存在于肝脏中并不断巡逻，以在遇到抗原时迅速引发免疫反应，并能有效介导对肝期疟原虫感染的保护。这一发现促使人们开发了免疫策略，即在脾脏中激活 T 细胞，然后将其困在肝脏中形成 T 细胞。在这里，我们确定了 PbRPL6，它是来自约氏疟原虫 ANKA 的假定 60S 核糖体蛋白 L6（RPL6）的一种 H2-K 限制性表位，是内源性肝 T 细胞产生和抵御疟疾的最佳抗原。针对 RPL6 的单次剂量疫苗接种可提供针对高剂量孢子虫挑战的有效和持久的杀菌免疫力。RPL6 在整个寄生虫生命周期中都有表达，跨越疟原虫物种，高度保守，具有很强的翻译潜力，是一种有前途的疫苗候选物。在恶性疟原虫 RPL6 中鉴定出一个广泛保守、免疫原性 HLA-A02:01 限制性表位，进一步证明了这一点。
