Nature Medicine
9, 729 - 735 (2003)
Published online: 25 May 2003; | doi:10.1038/nm881
Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humansSamuel J McConkey1, 7, William H H Reece1, 7, Vasee S Moorthy1, 7, Daniel Webster1, Susanna Dunachie1, Geoff Butcher2, Jenni M Vuola1, Tom J Blanchard3, Philip Gothard1, Kate Watkins1, Carolyn M Hannan1, Simone Everaere1, Karen Brown1, Kent E Kester4, James Cummings4, Jackie Williams4, D Gray Heppner4, Ansar Pathan1, Katie Flanagan1, Nirmalan Arulanantham1, Mark T M Roberts1, Michael Roy5, Geoffrey L Smith2, Joerg Schneider6, Tim Peto1, Robert E Sinden2, Sarah C Gilbert1
& Adrian V S Hill11
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. 2
Biological Sciences Department, Imperial College, London SW7 2AZ, UK. 3
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. 4
Malaria Vaccine Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 20910, USA. 5
PowderJect Vaccines, 585 Science Drive Suite C, Madison, Wisconsin 53711, USA. 6
Oxxon Pharmaccines, Oxford BioBusiness Centre, Oxford, OX4 4SS, UK. 7
These authors contributed equally to this work.
Correspondence should be addressed to Adrian V S Hill adrian.hill@imm.ox.ac.ukIn animals, effective immune responses against malignancies and against several infectious pathogens, including malaria, are mediated by T cells. Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally, followed by intradermal recombinant modified vaccinia virus Ankara (MVA), induces high frequencies of interferon (IFN)- -secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related adhesion protein (TRAP). These responses are five- to tenfold higher than the T-cell responses induced by the DNA vaccine or recombinant MVA vaccine alone, and produce partial protection manifest as delayed parasitemia after sporozoite challenge with a different strain of Plasmodium falciparum. Such heterologous prime-boost immunization approaches may provide a basis for preventative and therapeutic vaccination in humans.
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