Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults

Sci Transl Med. 2015 May 6;7(286):286re5. doi: 10.1126/scitranslmed.aaa2373.

Abstract

Protective immunity to the liver stage of the malaria parasite can be conferred by vaccine-induced T cells, but no subunit vaccination approach based on cellular immunity has shown efficacy in field studies. We randomly allocated 121 healthy adult male volunteers in Kilifi, Kenya, to vaccination with the recombinant viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA), both encoding the malaria peptide sequence ME-TRAP (the multiple epitope string and thrombospondin-related adhesion protein), or to vaccination with rabies vaccine as a control. We gave antimalarials to clear parasitemia and conducted PCR (polymerase chain reaction) analysis on blood samples three times a week to identify infection with the malaria parasite Plasmodium falciparum. On Cox regression, vaccination reduced the risk of infection by 67% [95% confidence interval (CI), 33 to 83%; P = 0.002] during 8 weeks of monitoring. T cell responses to TRAP peptides 21 to 30 were significantly associated with protection (hazard ratio, 0.24; 95% CI, 0.08 to 0.75; P = 0.016).

Publication types

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

MeSH terms

  • Adenoviruses, Simian / immunology*
  • Adult
  • Algorithms
  • Animals
  • Epitopes / immunology
  • Genotype
  • Humans
  • Immunization Schedule*
  • Kaplan-Meier Estimate
  • Kenia
  • Malaria Vaccines / therapeutic use*
  • Malaria, Falciparum / prevention & control*
  • Male
  • Pan troglodytes
  • Plasmodium falciparum
  • Polymerase Chain Reaction
  • Proportional Hazards Models
  • Protozoan Proteins / immunology*
  • Vaccinia virus / immunology*
  • Young Adult

Substances

  • Epitopes
  • Malaria Vaccines
  • Protozoan Proteins
  • thrombospondin-related adhesive protein, protozoan