title: Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults.
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).
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ogwang
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.
authors.forename: Domtila
authors.initials: D
authors.lastname: Kimani
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.|The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Edwards
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.|The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Roberts
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.
authors.forename: Jedidah
authors.initials: J
authors.lastname: Mwacharo
authors.affiliation: The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Georgina
authors.initials: G
authors.lastname: Bowyer
authors.affiliation: The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Carly
authors.initials: C
authors.lastname: Bliss
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.|The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Hodgson
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.
authors.forename: Patricia
authors.initials: P
authors.lastname: Njuguna
authors.affiliation: European Vaccine Initiative, 69120 Heidelberg, Germany.
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Viebig
authors.affiliation: ReiThera, Viale Città d'Europa 679, 00144 Rome, Italy.|CEINGE, Via Gaetano Salvatore 486, 80145 Naples, Italy.|Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Gitau
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.|The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Sandy
authors.initials: S
authors.lastname: Douglas
authors.affiliation: The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Illingworth
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.|Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Lawrie
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.|European Vaccine Initiative, 69120 Heidelberg, Germany.
authors.forename: Egeruan B
authors.initials: EB
authors.lastname: Imoukhuede
authors.affiliation: The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Ewer
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.|The Jenner Institute, Oxford OX3 7BN, UK.
authors.forename: Adrian V S
authors.initials: AVS
authors.lastname: Hill
authors.affiliation: Centre for Geographic Medicine Research, Kenya Medical Research Institute-Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya.|Centre for Clinical Vaccinology and Tropical Medicine, Oxford OX3 7BN, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
mesh_terms: D000261:Adenoviruses, Simian / Q000276:immunology*; D000328:Adult; D000465:Algorithms; D000818:Animals; D000939:Epitopes / Q000276:immunology; D005838:Genotype; D006801:Humans; D007115:Immunization Schedule; D053208:Kaplan-Meier Estimate; D007630:Kenya; D017780:Malaria Vaccines / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D002679:Pan troglodytes; D010963:Plasmodium falciparum; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D015800:Protozoan Proteins / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D000939:Epitopes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan