| Literature DB >> 32396839 |
Ana Maria Valencia-Hernandez1, Wei Yi Ng2, Nazanin Ghazanfari3, Sonia Ghilas3, Maria N de Menezes2, Lauren E Holz3, Cheng Huang4, Kieran English5, Myo Naung6, Peck Szee Tan7, Kirsteen M Tullett7, Thiago M Steiner3, Matthias H Enders8, Lynette Beattie3, Yu Cheng Chua2, Claerwen M Jones7, Anton Cozijnsen9, Vanessa Mollard9, Yeping Cai10, David G Bowen5, Anthony W Purcell7, Nicole L La Gruta7, Jose A Villadangos11, Tania de Koning-Ward12, Alyssa E Barry6, Winfried Barchet13, Ian A Cockburn10, Geoffrey I McFadden9, Stephanie Gras7, Mireille H Lahoud7, Patrick Bertolino5, Ralf B Schittenhelm4, Irina Caminschi14, William R Heath15, Daniel Fernandez-Ruiz16.
Abstract
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-A∗02:01-restricted epitope in P. falciparum RPL6.Entities:
Keywords: CD8 T cell; T cell memory; adaptive immmunity; antigen; dendritic cell targeting; epitope discovery; liver; malaria; tissue-resident memory T cell; vaccine
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Year: 2020 PMID： 32396839 DOI： 10.1016/j.chom.2020.04.010
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023