Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers

AIDS Res Hum Retroviruses. 2017 Aug;33(8):880-888. doi: 10.1089/AID.2016.0251. Epub 2017 Jan 27.

Abstract

We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p < .0001 and p < .05, respectively. The frequency of IFN-γ ELISpot responses increased to 95% against Gag or Env and 90% to both Gag and Env, p = .064 and p = .002, respectively. In conclusion, the HIV-DNA prime/HIV-MVA boost regimen elicited potent antibody and cellular immune responses with remarkable durability, and a third HIV-MVA immunization significantly boosted both antibody and cellular immune responses relative to the levels detected at the time of the third HIV-MVA, but not to higher levels than after the second HIV-MVA.

Keywords: DNA; HIV; MVA; immune response; vaccine.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Adaptive Immunity*
  • Adult
  • Antibody-Dependent Cell Cytotoxicity
  • Drug Carriers
  • Female
  • HIV Antibodies / blood
  • HIV-1 / immunology*
  • Healthy Volunteers
  • Humans
  • Immunization Schedule
  • Immunization, Secondary*
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Tanzania
  • Time Factors
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Vaccinia virus / genetics

Substances

  • AIDS Vaccines
  • Drug Carriers
  • HIV Antibodies
  • Vaccines, DNA
  • Vaccines, Synthetic
  • Interferon-gamma