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

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    Author
    Ewer, KJ; O'Hara, GA; Duncan, CJA; Collins, KA; Sheehy, SH; Reyes-Sandoval, A; Goodman, AL; Edwards, NJ; Elias, SC; Halstead, FD; ...
    Date
    2013-11-01
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Longley, Rhea
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Ewer, K. J., O'Hara, G. A., Duncan, C. J. A., Collins, K. A., Sheehy, S. H., Reyes-Sandoval, A., Goodman, A. L., Edwards, N. J., Elias, S. C., Halstead, F. D., Longley, R. J., Rowland, R., Poulton, I. D., Draper, S. J., Blagborough, A. M., Berrie, E., Moyle, S., Williams, N., Siani, L. ,... Hill, A. V. S. (2013). Protective CD8(+) T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. NATURE COMMUNICATIONS, 4 (1), https://doi.org/10.1038/ncomms3836.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254781
    DOI
    10.1038/ncomms3836
    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.

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