Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation.


Ewer, KJ; O'Hara, GA; Duncan, CJ; Collins, KA; Sheehy, SH; Reyes-Sandoval, A; Goodman, AL; Edwards, NJ; Elias, SC; Halstead, FD; Longley, RJ; Rowland, R; Poulton, ID; Draper, SJ; Blagborough, AM; Berrie, E; Moyle, S; Williams, N; Siani, L; Folgori, A; Colloca, S; Sinden, RE; Lawrie, AM; Cortese, R; Gilbert, SC; Nicosia, A; Hill, AV; (2013) Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun, 4. p. 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
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID: 24284865
Web of Science ID: 328027800004
URI: http://researchonline.lshtm.ac.uk/id/eprint/2352339

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