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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. © 2013 Macmillan Publishers Limited. All rights reserved.

Original publication

DOI

10.1038/ncomms3836

Type

Journal article

Journal

Nature Communications

Publication Date

28/11/2013

Volume

4