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

      Nature medicine

      Animals, Antigens, Protozoan, immunology, Humans, Immunization Schedule, Immunization, Secondary, Interferon-gamma, metabolism, Lymphocyte Activation, Malaria Vaccines, Malaria, Falciparum, prevention & control, therapy, Peptides, Plasmids, Plasmodium falciparum, genetics, Protozoan Proteins, T-Lymphocytes, Vaccines, DNA, Vaccines, Synthetic, Vaccinia virus

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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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          Author and article information

          Journal
          12766765
          10.1038/nm881

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