Journal article
mRNA vaccine against malaria tailored for liver-resident memory T cells
M Ganley, LE Holz, JJ Minnell, MN de Menezes, OK Burn, KCY Poa, SL Draper, K English, STS Chan, RJ Anderson, BJ Compton, AJ Marshall, A Cozijnsen, YC Chua, Z Ge, KJ Farrand, JC Mamum, C Xu, IA Cockburn, K Yui Show all
Nature Immunology | Published : 2023
Abstract
Malaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked on a messenger RNA (mRNA)-based vaccine strategy to induce liver Trm cells to prevent malaria. Although a standard mRNA vaccine was unable to generate liver Trm or protect against challenge with Plasmodium berghei sporozoites in mice, addition of an agonist that recruits T cell help from type..
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Awarded by Banting Research Foundation
Funding Acknowledgements
We thank the BRF at the Peter Doherty Institute, and the BRU and the Hugh Green Cytometry Centre at the Malaghan Institute of Medical Research for technical support. We thank D. Bowen for support of K.E., D. Godfrey for the CD1d-PBS-44 tetramers and the NIH tetramer core facility for the CD1d-PBS-57 tetramers. This work was supported by funding from the New Zealand Ministry of Business Innovation and Employment (contract RTVU1603 to Victoria University of Wellington) and the New Zealand Health Research Council (contract HRC-20/569 to Victoria University of Wellington and HRC14/1003 Independent Research Organisation Fund to the Malaghan Institute). K.C.Y.P. is supported by the Monash Graduate Scholarship and the Monash University MNHS Faculty International Tuition Scholarship. D.F.R. was supported by the National Health and Medical Research Council of Australia (NHMRC) 1139486, S.G. by NHMRC 1159272, P.B. and K.E. by NHMRC 1146677, W.R.H. by NHMRC 1154457, and W.R.H. and L.E.H. by NHMRC 2012701.