title: Safety and immunogenicity of the candidate tuberculosis vaccine MVA85A in West Africa.
abstract: BACKGROUND
  Vaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicity of this new vaccine in West African volunteers.
  
  
  RESULTS
  We vaccinated 21 healthy adult male subjects (11 BCG scar negative and 10 BCG scar positive) with MVA85A after screening for evidence of prior exposure to mycobacteria. We monitored them over six months, observing for clinical, haematological and biochemical adverse events, together with assessment of the vaccine induced cellular immune response using ELISPOT and flow cytometry. MVA85A was well tolerated with no significant adverse events. Mild local and systemic adverse events were consistent with previous UK trials. Marked immunogenicity was found whether individuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-naïve Gambians than previously studied BCG-naïve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis.
  
  
  CONCLUSIONS
  These data on the safety and immunogenicity of MVA85A in West Africa support its accelerated development as a promising booster vaccine for tuberculosis.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00423839.
authors.affiliation: Bacterial Diseases Programme, Tuberculosis Division, Medical Research Council Laboratories, Fajara, Banjul, The Gambia.
authors.forename: Roger H
authors.initials: RH
authors.lastname: Brookes
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hill
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Owiafe
authors.forename: Hannah B
authors.initials: HB
authors.lastname: Ibanga
authors.forename: David J
authors.initials: DJ
authors.lastname: Jeffries
authors.forename: Simon A
authors.initials: SA
authors.lastname: Donkor
authors.forename: Helen A
authors.initials: HA
authors.lastname: Fletcher
authors.forename: Abdulrahman S
authors.initials: AS
authors.lastname: Hammond
authors.forename: Christian
authors.initials: C
authors.lastname: Lienhardt
authors.forename: Richard A
authors.initials: RA
authors.lastname: Adegbola
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000328:Adult; D000354:Africa, Western; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D018579:Patient Selection; D012016:Reference Values; D012449:Safety; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D032581:Tuberculosis Vaccines; D000099192:CD69 Antigens