Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3836
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Funding
- UK MRC
- NIHR through the Oxford Biomedical Research Centre
- Wellcome Trust
- MRC [G0600424]
- MRC [G1000527, G0600424] Funding Source: UKRI
- Medical Research Council [G0600424, G1000527] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10233] Funding Source: researchfish
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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-gamma-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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