Valencia-Hernandez, Ana Maria, Ng, Wei Yi, Ghazanfari, Nazanin, Ghilas, Sonia, de Menezes, Maria N., Holz, Lauren E., Huang, Cheng, English, Kieran, Nuang, Myo, Tan, Peck Szee, Tullett, Kirsteen M., Steiner, Thiago M., Enders, Matthias H., Beattie, Lynette, Chua, Yu Cheng, Jones, Claerwen M., Cozijnsen, Anton, Mollard, Vanessa, Cai, Yeping, Bowen, David G., Purcell, Anthony W., La Gruta, Nicole L., Villadangos, Jose A., De Koning-ward, Tania, Barry, Alyssa E., Barchet, Winfried, Cockburn, Ian A., Mcfadden, Geoffrey I., Gras, Stephanie, Lahoud, Mireille H., Bertolino, Patrick, Schittenhelm, Ralf B., Caminschi, Irina, Heath, William R., and Fernandez-Ruiz, Daniel (2020) A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice. Cell Host & Microbe, 27 (6). 950-962.e7.

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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.

Item ID:	77327
Item Type:	Article (Research - C1)
ISSN:	1934-6069
Copyright Information:	© 2020 Elsevier Inc
Funders:	National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants:	NHMRC 1139486, NHMRC 1154457, NHMRC 1113293, NHMRC 1124706, NHMRC 1154502, NHMRC 1163090, NHMRC PRF 1137739, NHMRC SRF 1159272, ARC (CE140100011), ARC (FT170100174)
Date Deposited:	25 Jan 2023 05:51
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320402 Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies) @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 50%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 0% 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100%
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