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

Abstract

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.