Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans |
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| Authors: | McConkey Samuel J Reece William H H Moorthy Vasee S Webster Daniel Dunachie Susanna Butcher Geoff Vuola Jenni M Blanchard Tom J Gothard Philip Watkins Kate Hannan Carolyn M Everaere Simone Brown Karen Kester Kent E Cummings James Williams Jackie Heppner D Gray Pathan Ansar Flanagan Katie Arulanantham Nirmalan Roberts Mark T M Roy Michael Smith Geoffrey L Schneider Joerg Peto Tim Sinden Robert E Gilbert Sarah C Hill Adrian V S |
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| Institution: | Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. |
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| Abstract: | In 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)-gamma-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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