A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice

Ana Maria Valencia-Hernandez, Wei Yi Ng, Nazanin Ghazanfari, Sonia Ghilas, Maria N. de Menezes, Lauren E. Holz, Cheng Huang, Kieran English, Myo Naung, Peck Szee Tan, Kirsteen M. Tullett, Thiago M. Steiner, Matthias H. Enders, Lynette Beattie, Yu Cheng Chua, Claerwen M. Jones, Anton Cozijnsen, Vanessa Mollard, Yeping Cai, David G. BowenAnthony W. Purcell, Nicole L. La Gruta, Jose A. Villadangos, Tania de Koning-Ward, Alyssa E. Barry, Winfried Barchet, Ian A. Cockburn, Geoffrey I. McFadden, Stephanie Gras, Mireille H. Lahoud, Patrick Bertolino, Ralf B. Schittenhelm, Irina Caminschi, William R. Heath, Daniel Fernandez-Ruiz

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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-A02:01-restricted epitope in P. falciparum RPL6.

Original languageEnglish
Pages (from-to)950-962
Number of pages13
JournalCell Host and Microbe
Volume27
Issue number6
DOIs
Publication statusPublished - 10 Jun 2020

Keywords

  • adaptive immmunity
  • antigen
  • CD8 T cell
  • dendritic cell targeting
  • epitope discovery
  • liver
  • malaria
  • T cell memory
  • tissue-resident memory T cell
  • vaccine

Cite this

Valencia-Hernandez, A. M., Ng, W. Y., Ghazanfari, N., Ghilas, S., de Menezes, M. N., Holz, L. E., Huang, C., English, K., Naung, M., Tan, P. S., Tullett, K. M., Steiner, T. M., Enders, M. H., Beattie, L., Chua, Y. C., Jones, C. M., Cozijnsen, A., Mollard, V., Cai, Y., ... Fernandez-Ruiz, D. (2020). A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice. Cell Host and Microbe, 27(6), 950-962. https://doi.org/10.1016/j.chom.2020.04.010