Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: effects of dosage and route on safety and immunogenicity

Vaccine. 2007 Mar 1;25(11):2120-7. doi: 10.1016/j.vaccine.2006.11.016. Epub 2006 Nov 27.

Abstract

Background: Two parallel studies evaluated safety and immunogenicity of a prophylactic HIV-1 vaccine in 192 HIV-seronegative, low-risk volunteers. Modified vaccinia virus Ankara (MVA) and plasmid DNA (pTHr) expressed HIV-1 clade A gag p24 and p17 fused to a string of 25 overlapping CD8+ T cell epitopes (HIVA).

Methods: These studies compared intramuscular, subcutaneous, and intradermal MVA at dosage levels ranging from 5x10(6)-2.5x10(8) pfu. In Study IAVI-010, DNA vaccine was given as a prime at months 0 and 1, followed by MVA as a boost at months 5 and 8. In Study IAVI-011, MVA alone was given at months 0 and 2. Regular safety monitoring was performed. Immunogenicity was measured by the interferon (IFN)-gamma ELISPOT assay on peripheral blood mononuclear cells (PBMC).

Results: No serious adverse events were attributed to either vaccine; most adverse events were mild or moderate, although MVA resulted in some severe local reactions. Five vaccine recipients had at least one positive IFN-gamma ELISPOT response, but none were sustained.

Conclusion: This HIV-1 vaccine candidate was in general safe and well-tolerated. Local reactions were common, but tolerable. Detectable immune responses were infrequent.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / adverse effects*
  • AIDS Vaccines / immunology*
  • Adolescent
  • Adult
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • HIV-1 / immunology*
  • Humans
  • Immunization, Secondary
  • Injections, Intradermal
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Interferon-gamma / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Vaccination / methods
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / immunology*

Substances

  • AIDS Vaccines
  • Epitopes, T-Lymphocyte
  • MVA-HIVA vaccine
  • Vaccines, DNA
  • Interferon-gamma