title: Clinical assessment of a recombinant simian adenovirus ChAd63: a potent new vaccine vector.
abstract: BACKGROUND
  Vaccine development in human Plasmodium falciparum malaria has been hampered by the exceptionally high levels of CD8(+) T cells required for efficacy. Use of potently immunogenic human adenoviruses as vaccine vectors could overcome this problem, but these are limited by preexisting immunity to human adenoviruses.
  
  
  METHODS
  From 2007 to 2010, we undertook a phase I dose and route finding study of a new malaria vaccine, a replication-incompetent chimpanzee adenovirus 63 (ChAd63) encoding the preerythrocytic insert multiple epitope thrombospondin-related adhesion protein (ME-TRAP; n = 54 vaccinees) administered alone (n = 28) or with a modified vaccinia virus Ankara (MVA) ME-TRAP booster immunization 8 weeks later (n = 26). We observed an excellent safety profile. High levels of TRAP antigen-specific CD8(+) and CD4(+) T cells, as detected by interferon γ enzyme-linked immunospot assay and flow cytometry, were induced by intramuscular ChAd63 ME-TRAP immunization at doses of 5 × 10(10) viral particles and above. Subsequent administration of MVA ME-TRAP boosted responses to exceptionally high levels, and responses were maintained for up to 30 months postvaccination.
  
  
  CONCLUSIONS
  The ChAd63 chimpanzee adenovirus vector appears safe and highly immunogenic, providing a viable alternative to human adenoviruses as vaccine vectors for human use.
  
  
  BACKGROUND
  NCT00890019.
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine and the Jenner Institute Laboratories, University of Oxford, UK. geraldine.ohara@ndm.ox.ac.uk
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: O'Hara
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Ewer
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Collins
authors.forename: Sean C
authors.initials: SC
authors.lastname: Elias
authors.forename: Fenella D
authors.initials: FD
authors.lastname: Halstead
authors.forename: Anna L
authors.initials: AL
authors.lastname: Goodman
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Edwards
authors.forename: Arturo
authors.initials: A
authors.lastname: Reyes-Sandoval
authors.forename: Prudence
authors.initials: P
authors.lastname: Bird
authors.forename: Rosalind
authors.initials: R
authors.lastname: Rowland
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Sheehy
authors.forename: Ian D
authors.initials: ID
authors.lastname: Poulton
authors.forename: Claire
authors.initials: C
authors.lastname: Hutchings
authors.forename: Stephen
authors.initials: S
authors.lastname: Todryk
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Eleanor
authors.initials: E
authors.lastname: Berrie
authors.forename: Sarah
authors.initials: S
authors.lastname: Moyle
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.forename: Loredana
authors.initials: L
authors.lastname: Siani
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lawrie
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000261:Adenoviruses, Simian / Q000235:genetics / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D000939:Epitopes; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D007376:Interleukin-2; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma