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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.

Original publication

DOI

10.1038/ncomms3836

Type

Journal article

Journal

Nat Commun

Publication Date

2013

Volume

4

Keywords

Adenoviruses, Simian, Adolescent, Adult, Animals, Antibodies, Protozoan, CD8-Positive T-Lymphocytes, Female, Genetic Vectors, Humans, Immunity, Cellular, Immunization, Immunization, Secondary, Interferon-gamma, Leukocytes, Mononuclear, Malaria Vaccines, Malaria, Falciparum, Male, Middle Aged, Plasmodium falciparum, Protozoan Proteins, Vaccinia virus, Young Adult