Induction of CD4(+) T cell-dependent CD8(+) type 1 responses in humans by a malaria DNA vaccine

Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10817-22. doi: 10.1073/pnas.181123498. Epub 2001 Aug 28.

Abstract

We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-gamma responses were detected by enzyme-linked immunospot (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing class I and/or class II restricted epitopes, and were dependent on both CD8(+) and CD4(+) T cells. Overall, frequency of response was significantly greater after i.m. jet injection. CD8(+)-dependent cytotoxic T lymphocytes (CTL) were detected in 8/14 volunteers. Demonstration in humans of elicitation of the class I restricted IFN-gamma responses we believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • DNA, Protozoan / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / analysis
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control
  • Molecular Sequence Data
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / genetics*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*

Substances

  • Antigens, Protozoan
  • DNA, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • Vaccines, DNA
  • circumsporozoite protein, Protozoan
  • Interleukin-4
  • Interferon-gamma