RESUMEN
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.
Asunto(s)
Vacunas contra el SIDA/inmunología , Productos del Gen env/inmunología , Productos del Gen gag/inmunología , Vectores Genéticos/inmunología , Vacunas Atenuadas/inmunología , Virus de la Estomatitis Vesicular Indiana/inmunología , Vacunas contra el SIDA/administración & dosificación , Administración Intranasal , Animales , Anticuerpos Antivirales/sangre , Femenino , Productos del Gen env/genética , Productos del Gen env/metabolismo , Productos del Gen gag/genética , Productos del Gen gag/metabolismo , Vectores Genéticos/administración & dosificación , Anticuerpos Anti-VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , VIH-1/inmunología , Humanos , Inyecciones Intramusculares , Interferón gamma/biosíntesis , Macaca mulatta , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Linfocitos T/inmunología , Vacunación , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/genética , Virus de la Estomatitis Vesicular Indiana/genéticaRESUMEN
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.
