Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation

Nat Commun. 2013;4:2836. doi: 10.1038/ncomms3836.

Abstract

Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8(+) T cells, but not antibodies, correlates with sterile protection and delay in time to patency (P(corrected)=0.005). Vaccine-induced CD8(+) T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells.

Trial registration: ClinicalTrials.gov NCT00890760.

Publication types

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

MeSH terms

  • Adenoviruses, Simian / genetics
  • Adenoviruses, Simian / immunology*
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Protozoan / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • Humans
  • Immunity, Cellular
  • Immunization
  • Immunization, Secondary
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / prevention & control*
  • Male
  • Middle Aged
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology*
  • Young Adult

Substances

  • Antibodies, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • thrombospondin-related adhesive protein, protozoan
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00890760