An HIV-1 clade A/E DNA prime, recombinant fowlpox virus boost vaccine is safe, but non-immunogenic in a randomized phase I/IIa trial in Thai volunteers at low risk of HIV infection

Hum Vaccin. 2010 Oct;6(10):835-40. doi: 10.4161/hv.6.10.12635. Epub 2010 Oct 1.

Abstract

Background: Previously demonstrated safe and highly immunogenic in non-human primates, this study assessed DNA (pHIS-HIV-AE) prime, recombinant fowlpox (rFPV-HIV-AE) boost vaccines in humans.

Results: Eight participants (6 active vaccine, 2 placebo) received all vaccinations; local and systemic reactions were mild to moderate. The percentage CD4(+) and CD8(+) T cells responding to HIV-1 Gag antigens by ICS (mean ± SD) was 0.16 ± 0.12 and 0.10 ± 0.12 for active and 0.01 ± 0.01 and 0.00 ± 0.00 for placebo vaccine respectively. The percentage of T cells responding did not reach pre-defined thresholds to be considered positive responses. Consequently, the Data Safety Monitoring Board recommended cessation of further recruitment. Existing volunteers were followed to 52 weeks.

Methods: Vectors expressing homologous HIV-1 clade A/E gag, pol, env and regulatory genes or matched placebo were administered intramuscularly at weeks 0, 4, 8 (6 mg pHIS-HIV-AE) and week 12 (3.0 x 10(8) pfu rFPV-HIV-AE) in this randomized, double-blind, placebo-controlled phase I/IIa study in healthy Thai adults at low risk of HIV infection. Immunogenicity was determined by interferon-gamma and IL-2 expression using intracellular cytokine staining assay (ICS), 13 weeks after randomization. Interim analysis was performed when eight volunteers reached 16 weeks follow-up.

Conclusions: Vaccine candidates were generally well tolerated, but showed limited immunogenicity. Better vaccines and delivery systems are required.

Publication types

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

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / adverse effects*
  • AIDS Vaccines / immunology*
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / biosynthesis
  • Double-Blind Method
  • Drug Carriers
  • Female
  • Fowlpox virus / genetics
  • Genetic Vectors
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Human Experimentation
  • Humans
  • Immunization / methods*
  • Immunization, Secondary / methods
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Thailand
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / adverse effects*
  • Vaccines, DNA / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology

Substances

  • AIDS Vaccines
  • Cytokines
  • Drug Carriers
  • Placebos
  • Vaccines, DNA
  • Vaccines, Subunit
  • Vaccines, Synthetic