RESUMO
An experimental AIDS vaccine based on attenuated, recombinant vesicular stomatitis virus (rVSV), when administered by a combination of parenteral and mucosal routes, has proven effective at preventing AIDS in a rhesus macaque model (Rose NF, et al.: Cell 2001;106:539-549). In an effort to determine the optimal route of vaccine administration we evaluated the ability of rVSV-based vaccine vectors expressing HIV-1 Env and SIV Gag proteins, when given either intramuscularly (i.m.) or intranasally (i.n.), to elicit antigen-specific cellular and humoral immune responses, and to protect from a subsequent vaginal challenge with simian-human immunodeficiency virus (SHIV89.6P). Our results demonstrate that macaques vaccinated by the i.n. route developed significantly higher antigen-specific cellular immune responses as determined by MHC class I tetramer staining, IFN-gamma ELISPOT, and cytotoxic T cell assays. However, systemic and mucosal humoral immune responses did not vary significantly with the route of vaccine administration. Given the importance of cell-mediated immune responses in slowing AIDS progression, intranasal delivery of a VSV-based AIDS vaccine may be an optimal as well as practical route for vaccination and should be considered in design of clinical trials.
Assuntos
Vacinas contra a AIDS/imunologia , Produtos do Gene env/imunologia , Produtos do Gene gag/imunologia , Vetores Genéticos/imunologia , Vacinas Atenuadas/imunologia , Vírus da Estomatite Vesicular Indiana/imunologia , Vacinas contra a AIDS/administração & dosagem , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Feminino , Produtos do Gene env/genética , Produtos do Gene env/metabolismo , Produtos do Gene gag/genética , Produtos do Gene gag/metabolismo , Vetores Genéticos/administração & dosagem , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Humanos , Injeções Intramusculares , Interferon gama/biossíntese , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Linfócitos T/imunologia , Vacinação , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vírus da Estomatite Vesicular Indiana/genéticaRESUMO
A juvenile rhesus macaque presented with atrophy of the musculature of its left leg. Physical examination localized the problem to the coxofemoral joint. Radiography revealed changes consistent with Legg-Calvé-Perthes (LCP) disease. Femoral head ostectomy was performed, and the femoral head was submitted for histologic examination, results of which confirmed a diagnosis of LCP.