Ewer, Katie J; O'Hara, Geraldine A; Duncan, Christopher JA; Collins, Katharine A; Sheehy, Susanne H; Reyes-Sandoval, Arturo; Goodman, Anna L; Edwards, Nick J; Elias, Sean C; Halstead, Fenella D; +17 more... Longley, Rhea J; Rowland, Rosalind; Poulton, Ian D; Draper, Simon J; Blagborough, Andrew M; Berrie, Eleanor; Moyle, Sarah; Williams, Nicola; Siani, Loredana; Folgori, Antonella; Colloca, Stefano; Sinden, Robert E; Lawrie, Alison M; Cortese, Riccardo; Gilbert, Sarah C; Nicosia, Alfredo; Hill, Adrian VS; (2013) Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nature communications, 4 (1). 2836-. ISSN 2041-1723 DOI: https://doi.org/10.1038/ncomms3836
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Abstract
Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8(+) T cells, but not antibodies, correlates with sterile protection and delay in time to patency (P(corrected)=0.005). Vaccine-induced CD8(+) T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
PubMed ID | 24284865 |
ISI | 328027800004 |
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