barry-naturalpeptide-2020.pdf (2.2 MB)
A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice
journal contribution
posted on 2020-06-10, 00:00 authored by A M Valencia-Hernandez, W Y Ng, N Ghazanfari, S Ghilas, M N de Menezes, L E Holz, C Huang, K English, M Naung, P S Tan, K M Tullett, T M Steiner, M H Enders, L Beattie, Y C Chua, C M Jones, A Cozijnsen, V Mollard, Y Cai, D G Bowen, A W Purcell, N L La Gruta, J A Villadangos, Tania De Koning-WardTania De Koning-Ward, Alyssa BarryAlyssa Barry, W Barchet, I A Cockburn, G I McFadden, S Gras, M H Lahoud, P Bertolino, R B Schittenhelm, I Caminschi, W R Heath, D Fernandez-Ruiz© 2020 Elsevier Inc. 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.
History
Journal
Cell Host and MicrobeVolume
27Issue
6Pagination
950 - 962Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
Link to full text
ISSN
1931-3128eISSN
1934-6069Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
Categories
Keywords
Science & TechnologyLife Sciences & BiomedicineMicrobiologyParasitologyVirologyDENDRITIC CELLSPRECURSOR FREQUENCYIN-VIVOINFECTIONRESPONSESCTLTRANSCRIPTOMEREPERTOIREPROTECTIONANTIBODIESCD8 T cellT cell memoryadaptive immmunityantigendendritic cell targetingepitope discoverylivermalariatissue-resident memory T cellvaccineMicrobiology
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC