RESUMO
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.
Assuntos
Vacinas contra a AIDS/uso terapêutico , Vetores Genéticos , Soropositividade para HIV/terapia , HIV-1/genética , Imunoterapia , Vaccinia virus/genética , Vacinas contra a AIDS/administração & dosagem , Adulto , Sequência de Aminoácidos , Antirretrovirais/uso terapêutico , Anticorpos Antivirais/sangue , Especificidade de Anticorpos , Terapia Antirretroviral de Alta Atividade , Antígenos CD4/imunologia , Esquema de Medicação , Epitopos/imunologia , Produtos do Gene nef/genética , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/imunologia , Soropositividade para HIV/virologia , HIV-1/isolamento & purificação , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Alinhamento de Sequência , Linfócitos T Citotóxicos/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Vaccinia virus/imunologia , Carga Viral , Suspensão de Tratamento , Produtos do Gene nef do Vírus da Imunodeficiência HumanaRESUMO
We report on the first HLA B13-restricted minimal cytotoxic T lymphocyte (CTL) epitope RQDILDLWI (RI9, amino acids 106-114 in HIV-1 Nef). In most patients the frequency of RI9-specific CTL exceeded the number of CTL against other epitopes, indicating that RI9 is a dominant epitope in HLA B13-positive patients. Targeting this conserved Nef epitope may be an important factor for the published association of HLA B13 with a favourable course of HIV-1 infection.