Glycolipid-peptide vaccination induces liver-resident memory CD8+ T cells that protect against malaria
| Autor: | Lauren Holz, Yu Cheng Chua, Regan J Anderson, Sarah Draper, Benjamin Compton, Jasmine Li, Lukasz Kedzierski, Zhongfang Wang, Taryn Osmond, Kathryn Farrand, Patrick J Bertolino, David Bowen, Anton Cozijnsen, Vanessa Mollard, Geoffrey McFadden, Irina Caminschi, Mireille Lahoud, Katherine Kedzierska, Stephen John Turner, Dale Godfrey, Ian Hermans, Gavin Painter, William R Heath |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 202:196.27-196.27 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Liver resident-memory CD8+ T cells (TRM cells) provide important protection against liver-stage Plasmodium infections. Here, we show that a glycolipid-peptide conjugate vaccine designed to be cleaved in vivo to release the NKT cell agonist a-galactosylceramide (a-GalCer), together with a CD8+ T cell malarial epitope, efficiently induced intrahepatic malaria-specific T cells expressing canonical markers of liver TRM (CD69, CXCR6 and CD101). While sterile protection was achieved in a proportion of mice using a single vaccine dose, a combined prime-boost regimen induced higher numbers of liver TRM cells and more robust protection. Improved liver TRM cell generation and sterile immunity using a single dose of the vaccine were obtained in all mice by extending the C-and N-terminal residues of the minimal epitope, and by modifying the linker to enhance a-GalCer release. Our findings describe an ideal synthetic vaccine platform to generate large numbers of liver TRM cells that is potentially valuable for controlling a variety of hepatotropic infections. |
| Databáze: | OpenAIRE |
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