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

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

Journal article

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

AM Valencia-Hernandez, WY Ng, N Ghazanfari, S Ghilas, MN de Menezes, LE Holz, C Huang, K English, M Naung, PS Tan, KM Tullett, TM Steiner, MH Enders, L Beattie, YC Chua, CM Jones, A Cozijnsen, V Mollard, Y Cai, DG Bowen Show all

Cell Host and Microbe | CELL PRESS | Published : 2020

DOI: 10.1016/j.chom.2020.04.010

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 ag..

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University of Melbourne Researchers

Maria Nogueira de Menezes Author

Lauren Holz Author

Thiago M. Steiner Author

Lynette Beattie Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

We thank the members of the Mackay, Mueller and Heath labs for discussion and the Doherty's animal facility staff for mice husbandry. Work supported by the NHMRC of Australia; D.F.R. (NHMRC 1139486), W.R.H. (NHMRC 1154457, 1113293, and 1124706), I.C. (NHMRC 1124706), J.A.V. (NHMRC 1154502 and 1163090), A.W.P. (NHMRC PRF 1137739), and S.G. (NHMRC SRF 1159272). Work was also supported by the Australian Research Council; N.G., S.G., L.E.H., T.M.S., M.H.E., L.B., W.R.H., D.F.R. (CE140100011) and N.L.G. (FT170100174).