Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles

J Infect Dis. 2011 Mar 1;203(5):610-9. doi: 10.1093/infdis/jiq105. Epub 2011 Jan 31.

Abstract

Background: Recombinant DNA and modified vaccinia virus Ankara (rMVA) vaccines represent a promising approach to an HIV/AIDS vaccine. This Phase 1 clinical trial compared the safety and immunogenicity of a rMVA vaccine administered with and without DNA vaccine priming

Methods: GeoVax pGA2/JS7 DNA (D) and MVA/HIV62 (M) vaccines encode noninfectious virus-like particles. Intramuscular needle injections were used to deliver placebo, 2 doses of DNA followed by 2 doses of rMVA (DDMM), one dose of DNA followed by 2 doses of rMVA (DMM), or 3 doses of rMVA (MMM) to HIV-seronegative participants.

Results: Local and systemic symptoms were mild or moderate. Immune response rates for CD4 + and CD8 + T cells were highest in the DDMM group and lowest in the MMM group (77% vs 43% CD4 + and 42% vs 17% CD8 +). In contrast, response rates for Env binding and neutralizing Ab were highest in the MMM group. The DMM group had intermediate response rates. A 1/10th-dose DDMM regimen induced similar T cell but reduced Ab response rates compared with the full-dose DDMM.

Conclusions: MVA62 was well tolerated and elicited different patterns of T cell and Ab responses when administered alone or in combination with the JS7 DNA vaccine.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines / immunology*
  • Adolescent
  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Double-Blind Method
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Vectors
  • HIV Antibodies / biosynthesis
  • HIV Antibodies / blood
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • United States
  • Vaccines, DNA / immunology*
  • Vaccines, DNA / standards
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology*
  • Young Adult

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • Placebos
  • Vaccines, DNA