Journal article

Glycolipid-peptide vaccination induces liver-resident memory CD8( ) T cells that protect against rodent malaria

Lauren E Holz, Yu Cheng Chua, Maria N de Menezes, Regan J Anderson, Sarah L Draper, Benjamin J Compton, Susanna TS Chan, Juby Mathew, Jasmine Li, Lukasz Kedzierski, Zhongfang Wang, Lynette Beattie, Matthias H Enders, Sonia Ghilas, Rose May, Thiago M Steiner, Joshua Lange, Daniel Fernandez-Ruiz, Ana Maria Valencia-Hernandez, Taryn L Osmond Show all

Science Immunology | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2020

Abstract

Liver resident-memory CD8+ T cells (TRM cells) can kill liver-stage Plasmodium-infected cells and prevent malaria, but simple vaccines for generating this important immune population are lacking. Here, we report the development of a fully synthetic self-adjuvanting glycolipid-peptide conjugate vaccine designed to efficiently induce liver TRM cells. Upon cleavage in vivo, the glycolipid-peptide conjugate vaccine releases an MHC I-restricted peptide epitope (to stimulate Plasmodium-specific CD8+ T cells) and an adjuvant component, the NKT cell agonist α-galactosylceramide (α-GalCer). A single dose of this vaccine in mice induced substantial numbers of intrahepatic malaria-specific CD8+ T cells..

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Grants

Awarded by Australian Research Council


Awarded by National Health and Medical Research Council (NHMRC)


Awarded by New Zealand Ministry of Business Innovation and Employment


Awarded by NHMRC


Funding Acknowledgements

This work was supported by the Australian Research Council (CE140100011), National Health and Medical Research Council (NHMRC; 1113293), New Zealand Ministry of Business Innovation and Employment (RTVU1603), and Avalia Immunotherapies. K.K., D.I.G, and W.R.H. are NHMRC Senior Principal Research Fellows (1117766 and 1154457).