title: Translating the immunogenicity of prime-boost immunization with ChAd63 and MVA ME-TRAP from malaria naive to malaria-endemic populations.
abstract: To induce a deployable level of efficacy, a successful malaria vaccine would likely benefit from both potent cellular and humoral immunity. These requirements are met by a heterologous prime-boost immunization strategy employing a chimpanzee adenovirus vector followed by modified vaccinia Ankara (MVA), both encoding the pre-erythrocytic malaria antigen ME-thrombospondin-related adhesive protein (TRAP), with high immunogenicity and significant efficacy in UK adults. We undertook two phase 1b open-label studies in adults in Kenya and The Gambia in areas of similar seasonal malaria transmission dynamics and have previously reported safety and basic immunogenicity data. We now report flow cytometry and additional interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) data characterizing pre-existing and induced cellular immunity as well as anti-TRAP IgG responses. T-cell responses induced by vaccination averaged 1,254 spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) across both trials and flow cytometry revealed cytokine production from both CD4(+) and CD8(+) T cells with the frequency of CD8(+) IFN-γ-secreting monofunctional T cells (previously shown to associate with vaccine efficacy) particularly high in Kenyan adults. Immunization with ChAd63 and MVA ME-TRAP induced strong cellular and humoral immune responses in adults living in two malaria-endemic regions of Africa. This prime-boost approach targeting the pre-erythrocytic stage of the malaria life-cycle is now being assessed for efficacy in a target population.
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Domtila
authors.initials: D
authors.lastname: Kimani
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Ya Jankey
authors.initials: YJ
authors.lastname: Jagne
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Momodou
authors.initials: M
authors.lastname: Cox
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Eva
authors.initials: E
authors.lastname: Kimani
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Carly M
authors.initials: CM
authors.lastname: Bliss
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Gitau
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ogwang
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Muhammed O
authors.initials: MO
authors.lastname: Afolabi
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Georgina
authors.initials: G
authors.lastname: Bowyer
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Collins
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Edwards
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, UK.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Hodgson
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, UK.
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Miguel G
authors.initials: MG
authors.lastname: Knight
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Abdoulie
authors.initials: A
authors.lastname: Drammeh
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, UK.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Anagnostou
authors.affiliation: Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Berrie
authors.affiliation: Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Moyle
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Peninah
authors.initials: P
authors.lastname: Soipei
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Okebe
authors.affiliation: Okairòs AG, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.affiliation: 1] Okairòs AG, Rome, Italy [2] CEINGE, Naples, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.affiliation: European Vaccine Initiative, UniversitätsKlinikum Heidelberg, Heidelberg, Germany.
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Viebig
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Roberts
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, UK.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lawrie
authors.affiliation: 1] Okairòs AG, Rome, Italy [2] CEINGE, Naples, Italy [3] Department of Biochemistry and Medical Biotechnology, University Federico II Naples, Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: European Vaccine Initiative, UniversitätsKlinikum Heidelberg, Heidelberg, Germany.
authors.forename: Egeruan B
authors.initials: EB
authors.lastname: Imoukhuede
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
authors.forename: Roma
authors.initials: R
authors.lastname: Chilengi
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Kalifa
authors.initials: K
authors.lastname: Bojang
authors.affiliation: 1] Medical Research Council Unit, Fajara, The Gambia [2] Department of Immunology, Monash University, Melbourne, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.affiliation: 1] The Jenner Institute Laboratories, University of Oxford, Oxford, UK [2] Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, UK.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: 1] Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya [2] Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Ewer
mesh_terms: D000261:Adenoviruses, Simian / Q000235:genetics*; D000328:Adult; D019353:Endemic Diseases; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D007117:Immunization, Secondary; D007630:Kenya / Q000453:epidemiology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D006113:United Kingdom; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D017780:Malaria Vaccines; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan