Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara

Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4836-41. doi: 10.1073/pnas.0406381102. Epub 2005 Mar 21.

Abstract

Malaria is a major global health problem for which an effective vaccine is required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage malaria antigens have been shown to be powerfully immunogenic for T cells and capable of inducing partial protection against experimental malaria challenge in humans, manifested as a delay in time to patent parasitemia. Here, we report that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months. Protection at 20 months was associated with persisting memory but not effector T cell responses. The protective efficacy of various immunization regimes correlated with the magnitude of induced immune responses, supporting the strategy of maximizing durable T cell immunogenicity to develop more effective liver-stage vaccines against Plasmodium falciparum malaria.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fowlpox virus / genetics
  • Fowlpox virus / immunology
  • Humans
  • Immunity, Cellular / immunology
  • Immunization, Secondary / methods*
  • Immunoglobulin G / immunology
  • Immunologic Memory / immunology
  • Interferon-gamma / blood
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / prevention & control*
  • Male
  • Middle Aged
  • Plasmids / genetics
  • Plasmids / immunology
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • T-Lymphocytes / immunology*
  • Vaccines, DNA / immunology*
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology

Substances

  • Immunoglobulin G
  • Malaria Vaccines
  • Protozoan Proteins
  • Vaccines, DNA
  • thrombospondin-related adhesive protein, protozoan
  • Interferon-gamma