title: PedVacc 002: a phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi.
abstract: BACKGROUND
  A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants.
  
  
  METHODS
  A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya.
  
  
  METHODS
  Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines.
  
  
  RESULTS
  Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p=0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p=0.05).
  
  
  CONCLUSIONS
  This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens.
authors.affiliation: Department of Pediatrics and Child Health, University of Nairobi, PO Box 19676, 00202 Nairobi, Kenya.
authors.forename: Irene N
authors.initials: IN
authors.lastname: Njuguna
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA 98104, USA.
authors.forename: Gwen
authors.initials: G
authors.lastname: Ambler
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-17177 Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Reilly
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ondondo
authors.affiliation: Department of Pediatrics and Child Health, University of Nairobi, PO Box 19676, 00202 Nairobi, Kenya.
authors.forename: Mercy
authors.initials: M
authors.lastname: Kanyugo
authors.affiliation: Department of Pediatrics and Child Health, University of Nairobi, PO Box 19676, 00202 Nairobi, Kenya.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lohman-Payne
authors.affiliation: Department of Clinical Medicine and Therapeutics, University of Nairobi, PO Box 19676, 00202 Nairobi, Kenya.
authors.forename: Christine
authors.initials: C
authors.lastname: Gichuhi
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Borthwick
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Antony
authors.initials: A
authors.lastname: Black
authors.affiliation: Statistics and Data Management Department, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Shams-Rony
authors.initials: SR
authors.lastname: Mehedi
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-17177 Stockholm, Sweden.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pediatrics and Child Health, University of Nairobi, PO Box 19676, 00202 Nairobi, Kenya.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.affiliation: Department of Pediatrics and Child Health, University of Nairobi, PO Box 19676, 00202 Nairobi, Kenya.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Chohan
authors.affiliation: Departments of Pediatrics, Medicine, Epidemiology, and Global Health, University of Washington, Seattle, WA 98104, USA.
authors.forename: Grace C
authors.initials: GC
authors.lastname: John-Stewart
authors.affiliation: KAVI-Institute of Clinical Research, University of Nairobi, PO Box 19676, 00202 Nairobi, Kenya.
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; The Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK. Electronic address: tomas.hanke@ndm.ox.ac.uk.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007371:Interferon-gamma / Q000276:immunology; D007630:Kenya; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D015483:HIV Antibodies; C573415:IFNG protein, human; C505104:MVA-HIVA vaccine; D019444:Vaccines, DNA; D007371:Interferon-gamma
keywords: EPI vaccines; Exposed-uninfected infants; HIV-1; Infant vaccine trial in Africa; KEPI vaccines; Modified vaccinia virus Ankara (MVA); Pediatric HIV-1 vaccines