RESUMEN
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.
Asunto(s)
Vacunas contra el SIDA/uso terapéutico , Vectores Genéticos , Seropositividad para VIH/terapia , VIH-1/genética , Inmunoterapia , Virus Vaccinia/genética , Vacunas contra el SIDA/administración & dosificación , Adulto , Secuencia de Aminoácidos , Antirretrovirales/uso terapéutico , Anticuerpos Antivirales/sangre , Especificidad de Anticuerpos , Terapia Antirretroviral Altamente Activa , Antígenos CD4/inmunología , Esquema de Medicación , Epítopos/inmunología , Productos del Gen nef/genética , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/inmunología , Seropositividad para VIH/virología , VIH-1/aislamiento & purificación , Humanos , Recuento de Linfocitos , Persona de Mediana Edad , Datos de Secuencia Molecular , Alineación de Secuencia , Linfocitos T Citotóxicos/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/uso terapéutico , Virus Vaccinia/inmunología , Carga Viral , Privación de Tratamiento , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
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.