title: A phase Ia study to assess the safety and immunogenicity of new malaria vaccine candidates ChAd63 CS administered alone and with MVA CS.
abstract: BACKGROUND
  Plasmodium falciparum (P. falciparum) malaria remains a significant cause of mortality and morbidity throughout the world. Development of an effective vaccine would be a key intervention to reduce the considerable social and economic impact of malaria.
  
  
  METHODS
  We conducted a Phase Ia, non-randomized, clinical trial in 24 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding the circumsporozoite protein (CS) of P. falciparum.
  
  
  RESULTS
  ChAd63-MVA CS administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to CS. With a priming ChAd63 CS dose of 5×109 vp responses peaked at a mean of 1947 SFC/million PBMC (median 1524) measured by ELIspot 7 days after the MVA boost and showed a mixed CD4+/CD8+ phenotype. With a higher priming dose of ChAd63 CS dose 5×1010 vp T cell responses did not increase (mean 1659 SFC/million PBMC, median 1049). Serum IgG responses to CS were modest and peaked at day 14 post ChAd63 CS (median antibody concentration for all groups at day 14 of 1.3 µg/ml (range 0-11.9), but persisted throughout late follow-up (day 140 median antibody concentration groups 1B & 2B 0.9 µg/ml (range 0-4.7).
  
  
  CONCLUSIONS
  ChAd63-MVA is a safe and highly immunogenic delivery platform for the CS antigen in humans which warrants efficacy testing.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01450280.
authors.affiliation: Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Eoghan
authors.initials: E
authors.lastname: de Barra
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Hodgson
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Ewer
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom.
authors.forename: Carly M
authors.initials: CM
authors.lastname: Bliss
authors.affiliation: Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Kerrie
authors.initials: K
authors.lastname: Hennigan
authors.affiliation: Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Ann
authors.initials: A
authors.lastname: Collins
authors.affiliation: Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Berrie
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lawrie
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.affiliation: Okairòs AG, Rome, Italy; CEINGE, Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: McConkey
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000261:Adenoviruses, Simian / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D008875:Middle Aged; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; C560489:MVA vaccine; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; C041595:circumsporozoite protein, Protozoan