Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption

Antivir Ther. 2005;10(2):285-300.


The safety and immunogenicity of an HIV-1 nef-expressing modified vaccinia virus Ankara (MVA) was investigated in 14 HIV-1-positive patients (CD4 >400/microl) on highly active antiretroviral therapy (HAART). Patients were vaccinated at weeks 0, 4 and 16, followed by interruption of HAART at week 18. MVA-nef was well-tolerated except for local reactions, with only mild systemic side effects reported in a few patients. Vaccination with MVA-nef was associated with recognition of new HIV-1 T-cell epitopes (cytotoxic T-lymphocyte epitopes in 9/14 patients, CD4 epitope/recombinant Nef protein in 2/14) and an increase in CD4+ and CD8+ T cells. All patients had been vaccinated against smallpox and a strong T-cell and antibody response to MVA was induced in all patients. After interruption of HAART, viral load rebounded in all patients, but after a median time of 36 (4-76) weeks in 9/14 patients, viraemia remained below the pre-HAART viral load and CD4 counts stayed above the pre-HAART levels. While six patients have remained off therapy for a median time of 64 (57-76) weeks, HAART was resumed in 8/14 patients after a median treatment interruption time of 15 (4-38) weeks. This study has demonstrated that MVA-nef is safe and immunogenic in HIV-1-infected subjects and has provided encouraging data on the potential of therapeutic vaccinations.

Publication types

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

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / therapeutic use*
  • Adult
  • Amino Acid Sequence
  • Anti-Retroviral Agents / therapeutic use
  • Antibodies, Viral / blood
  • Antibody Specificity
  • Antiretroviral Therapy, Highly Active
  • CD4 Antigens / immunology
  • Drug Administration Schedule
  • Epitopes / immunology
  • Gene Products, nef / genetics
  • Genetic Vectors*
  • HIV Seropositivity / drug therapy
  • HIV Seropositivity / immunology
  • HIV Seropositivity / therapy*
  • HIV Seropositivity / virology
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Immunotherapy*
  • Lymphocyte Count
  • Middle Aged
  • Molecular Sequence Data
  • Sequence Alignment
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • Vaccinia virus / genetics*
  • Vaccinia virus / immunology
  • Viral Load
  • Withholding Treatment
  • nef Gene Products, Human Immunodeficiency Virus


  • AIDS Vaccines
  • Anti-Retroviral Agents
  • Antibodies, Viral
  • CD4 Antigens
  • Epitopes
  • Gene Products, nef
  • Vaccines, Synthetic
  • nef Gene Products, Human Immunodeficiency Virus