Protective CD8(+) T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
AuthorEwer, KJ; O'Hara, GA; Duncan, CJA; Collins, KA; Sheehy, SH; Reyes-Sandoval, A; Goodman, AL; Edwards, NJ; Elias, SC; Halstead, FD; ...
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sLongley, Rhea
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsEwer, 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 StatusOpen Access
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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