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A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice.
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.chom.2020.04.010
Ana Maria Valencia-Hernandez 1 , Wei Yi Ng 2 , Nazanin Ghazanfari 3 , Sonia Ghilas 3 , Maria N de Menezes 2 , Lauren E Holz 3 , Cheng Huang 4 , Kieran English 5 , Myo Naung 6 , Peck Szee Tan 7 , Kirsteen M Tullett 7 , Thiago M Steiner 3 , Matthias H Enders 8 , Lynette Beattie 3 , Yu Cheng Chua 2 , Claerwen M Jones 7 , Anton Cozijnsen 9 , Vanessa Mollard 9 , Yeping Cai 10 , David G Bowen 5 , Anthony W Purcell 7 , Nicole L La Gruta 7 , Jose A Villadangos 11 , Tania de Koning-Ward 12 , Alyssa E Barry 6 , Winfried Barchet 13 , Ian A Cockburn 10 , Geoffrey I McFadden 9 , Stephanie Gras 7 , Mireille H Lahoud 7 , Patrick Bertolino 5 , Ralf B Schittenhelm 4 , Irina Caminschi 7 , William R Heath 3 , Daniel Fernandez-Ruiz 3
Affiliation  

Liver-resident memory CD8+ T (TRM) 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 TRM cells. Here, we identify PbRPL6120-127, a H2-Kb-restricted epitope from the putative 60S ribosomal protein L6 (RPL6) of Plasmodium berghei ANKA, as an optimal antigen for endogenous liver TRM 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.



中文翻译:

疟原虫核糖体蛋白RPL6中的天然肽抗原赋予小鼠抗疟疾的肝TRM细胞介导的免疫力。

肝驻留记忆CD8 + T(T RM)细胞保留在肝脏中并不断巡逻,以在遇到抗原时引发快速免疫力,并可以介导针对肝阶段疟原虫感染的有效保护。这一发现促进了免疫策略的发展,其中T细胞在脾脏中被激活,然后被困在肝脏中以形成T RM细胞。在这里,我们确定PbRPL6 120-127,一个H2-K b -restricted表位的推定60S核糖体蛋白L6(RPL6)伯氏疟原虫ANKA,作为用于内源性肝T时的最佳抗原RM细胞生成和抗疟疾。靶向RPL6的单剂量疫苗接种可针对高剂量子孢子挑战提供有效且延长的杀菌免疫力。RPL6在整个疟原虫的整个生命周期中,在疟原虫物种中表达并高度保守,具有作为疫苗候选者的强大翻译潜能。鉴定恶性疟原虫RPL6中广泛保守的,具有免疫原性的HLA-A * 02:01限制的表位进一步证明了这一点。

更新日期:2020-05-11
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