Enhanced T-cell Immunogenicity of Plasmid DNA Vaccines Boosted by Recombinant Modified Vaccinia Virus Ankara in Humans

Nat Med. 2003 Jun;9(6):729-35. doi: 10.1038/nm881. Epub 2003 May 25.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antigens, Protozoan
  • Malaria Vaccines
  • Peptides
  • Protozoan Proteins
  • Vaccines, DNA
  • Vaccines, Synthetic
  • thrombospondin-related adhesive protein, protozoan
  • Interferon-gamma