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Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans

Nature Medicine volume 9, pages 729–735 (2003)Cite this article

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)-γ-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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Figure 1: Plasmid DNA vaccine encoding ME-TRAP.
Figure 2: ELISPOT responses to pools of peptides 7 d after various vaccination regimens.
Figure 3: Characteristics of induced T-cell responses and protective efficacy.

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Acknowledgements

We acknowledge the contribution made to this research by the subjects who volunteered to participate in this study. We thank M. Plebanski, A. J. McMichael, R. J. Anderson, P. Degano, M. Pinder, G. Cooke, D. Crook, A. Neubert and S. Correa for discussions and assistance, and the Wellcome Trust for funding the work. S.J.M. and V.S.M. are Wellcome Trust Tropical Medicine Fellows, and G.L.S. and A.V.S.H. are Wellcome Trust Principal Research Fellows.

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Author notes

  1. Samuel J McConkey, William H H Reece and Vasee S Moorthy: These authors contributed equally to this work.

Authors and Affiliations

  1. Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Samuel J McConkey, William H H Reece, Vasee S Moorthy, Daniel Webster, Susanna Dunachie, Jenni M Vuola, Philip Gothard, Kate Watkins, Carolyn M Hannan, Simone Everaere, Karen Brown, Ansar Pathan, Katie Flanagan, Nirmalan Arulanantham, Mark T M Roberts, Tim Peto, Sarah C Gilbert & Adrian V S Hill

  2. Biological Sciences Department, Imperial College, London, SW7 2AZ, UK

    Geoff Butcher, Geoffrey L Smith & Robert E Sinden

  3. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Tom J Blanchard

  4. Malaria Vaccine Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, 20910, Maryland, USA

    Kent E Kester, James Cummings, Jackie Williams & D Gray Heppner

  5. PowderJect Vaccines, 585 Science Drive Suite C, Madison, 53711, Wisconsin, USA

    Michael Roy

  6. Oxxon Pharmaccines, Oxford BioBusiness Centre, Oxford, OX4 4SS, UK

    Joerg Schneider

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  1. Samuel J McConkey
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Corresponding author

Correspondence to Adrian V S Hill.

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Competing interests

M.R.is an employee of Powderject Vaccines,which manufactures the needleless delivery device.J.S.is an employee and cofounder of Oxxon Pharmaccines,Ltd.,which is developing prime-boost vaccines for therapeutic applications using MVA. A.V.S.H.and G.L.S.are cofounders of and consultants to Oxxon Pharmaccines,Ltd.

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McConkey, S., Reece, W., Moorthy, V. et al. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat Med 9, 729–735 (2003). https://doi.org/10.1038/nm881

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