Publications & Reports

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

Valencia-Hernandez AM, Ng WY, Ghazanfari N, Ghilas S, de Menezes MN, Holz LE, Huang C, English K, Naung M, Tan PS, Tullett KM, Steiner TM, Enders MH, Beattie L, Chua YC, Jones CM, Cozijnsen A, Mollard V, Cai Y, Bowen DG, Purcell AW, La Gruta NL, Villadangos JA, de Koning-Ward T, Barry AE, Barchet W, Cockburn IA, McFadden GI, Gras S, Lahoud MH, Bertolino P, Schittenhelm RB, Caminschi I, Heath WR, Fernandez-Ruiz D

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-K(b)-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.

Link to publisher’s web site

Publication

  • Journal: Cell Host & Microbe
  • Published: 06/05/2020
  • Volume: 27
  • Issue: 6
  • Pagination: 950-962.e7

Author

Program

Health Issue