A Phase I Randomized Clinical Trial of Candidate Human Immunodeficiency Virus Type 1 Vaccine MVA.HIVA Administered to Gambian Infants

PLoS One. 2013 Oct 24;8(10):e78289. doi: 10.1371/journal.pone.0078289. eCollection 2013.

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.

Trial design: 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.

Trial registration: ClinicalTrials.gov NCT00982579. The Pan African Clinical Trials Registry PACTR2008120000904116.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Antibody Formation / immunology
  • Breast Feeding
  • Female
  • Gambia
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunization, Secondary / methods
  • Infant
  • Interferon-gamma / immunology
  • Male
  • Milk, Human / immunology
  • Milk, Human / virology
  • Vaccination / methods
  • Vaccines, DNA / immunology
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology*

Substances

  • AIDS Vaccines
  • MVA-HIVA vaccine
  • Vaccines, DNA
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00982579