RESUMO
We have previously reported that therapeutic immunization by intramuscular injection of optimized plasmid DNAs encoding SIV antigens effectively induces immune responses able to reduce viremia in antiretroviral therapy (ART)-treated SIVmac251-infected Indian rhesus macaques. We subjected such therapeutically immunized macaques to a second round of therapeutic vaccination using a combination of plasmids expressing SIV genes and the IL-15/IL-15 receptor alpha as molecular adjuvant, which were delivered by the more efficacious in vivo constant-current electroporation. A very strong induction of antigen-specific responses to Gag, Env, Nef, and Pol, during ART (1.2-1.6% of SIV-specific T cells in the circulating T lymphocytes) was obtained with the improved vaccination method. Immunological responses were characterized by the production of IFN-gamma, IL-2, and TNF-alpha either alone, or in combination as double or triple cytokine positive multifunctional T cells. A significant induction of CD4(+) T cell responses, mainly targeting Gag, Nef, and Pol, as well as of CD8(+) T cells, mainly targeting Env, was found in both T cells with central memory and effector memory markers. After release from ART, the animals showed a virological benefit with a further approximately 1 log reduction in viremia. Vaccination with plasmid DNAs has several advantages over other vaccine modalities, including the possibility for repeated administration, and was shown to induce potent, efficacious, and long-lasting recall immune responses. Therefore, these data support the concept of adding DNA vaccination to the HAART regimen to boost the HIV-specific immune responses.
Assuntos
Imunização Secundária , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vacinas de DNA/imunologia , Viremia/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos Virais/imunologia , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Eletroporação , Imunidade Celular , Imunidade Humoral , Interleucina-15/imunologia , Macaca mulatta , Plasmídeos , Receptores de Interleucina-15/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Carga Viral , Viremia/imunologiaRESUMO
A HIV-positive patient, 3 months after the treatment initiation with lopinavir-/ritonavir (LPV/r) acquired macroglossia. The tongue biopsy revealed mature adipose tissue accumulated into submucosa. The drug was discontinued and the patient showed a significant improvement. This case is the first case in the medical literature of acquired macroglossia because of LPV/r, a drug causing changes in body fat composition.
