title: A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants.
abstract: BACKGROUND
  A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.
  
  
  METHODS
  We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.
  
  
  METHODS
  Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI) vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.
  
  
  RESULTS
  From March to October 2010, 48 infants (24 vaccine and 24 no-treatment) were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9%) and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.
  
  
  CONCLUSIONS
  A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and/or other infections in this age group.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00982579. The Pan African Clinical Trials Registry PACTR2008120000904116.
authors.affiliation: Vaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Muhammed O
authors.initials: MO
authors.lastname: Afolabi
authors.forename: Jorjoh
authors.initials: J
authors.lastname: Ndure
authors.forename: Abdoulie
authors.initials: A
authors.lastname: Drammeh
authors.forename: Fatoumatta
authors.initials: F
authors.lastname: Darboe
authors.forename: Shams-Rony
authors.initials: SR
authors.lastname: Mehedi
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Nicola
authors.initials: N
authors.lastname: Borthwick
authors.forename: Antony
authors.initials: A
authors.lastname: Black
authors.forename: Gwen
authors.initials: G
authors.lastname: Ambler
authors.forename: Grace C
authors.initials: GC
authors.lastname: John-Stewart
authors.forename: Marie
authors.initials: M
authors.lastname: Reilly
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D001942:Breast Feeding; D005260:Female; D005714:Gambia; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008895:Milk, Human / Q000276:immunology / Q000821:virology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; C505104:MVA-HIVA vaccine; D019444:Vaccines, DNA; D007371:Interferon-gamma