RESUMO
Heterologous prime/boost regimens have the potential for raising high levels of immune responses. Here we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster controlled a highly pathogenic immunodeficiency virus challenge in a rhesus macaque model. Both the DNA and rMVA components of the vaccine expressed multiple immunodeficiency virus proteins. Two DNA inoculations at 0 and 8 weeks and a single rMVA booster at 24 weeks effectively controlled an intrarectal challenge administered 7 months after the booster. These findings provide hope that a relatively simple multiprotein DNA/MVA vaccine can help to control the acquired immune deficiency syndrome epidemic.
Assuntos
Vacinas contra a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Vacinas de DNA/imunologia , Vacinas contra a AIDS/administração & dosagem , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Centro Germinativo/imunologia , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , HIV-1/genética , HIV-1/imunologia , HIV-1/fisiologia , Imunidade nas Mucosas , Imunização Secundária , Memória Imunológica , Interferon gama/biossíntese , Linfonodos/imunologia , Macaca mulatta , Vacinas contra a SAIDS/administração & dosagem , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Linfócitos T/imunologia , Vacinas de DNA/administração & dosagem , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Vaccinia virus/imunologia , Carga ViralRESUMO
Periglomerular and interstitial fibrosis were the earliest renal lesions in 21 Norwegian Elkhound (NE) dogs with familial renal disease. Histopathologic study did not reveal the cause of the disease, and light microscopy did not show renal lesions different from nonfamilial renal lesions commonly observed in dogs. Histopathologic evaluation was reliable for detecting disease in NE dogs prior to onset of isosthenuria and azotemia. Results of glomerular counts, determining kidney size, and dissection of the nephron indicated that nephron numbers and size were adequate early in the disease, but that numbers decreased as the disease progressed. Electron microscopic and immunofluorescent studies were not suggestive of an immune basis of the renal disease, nor did histopathologic or angiographic studies indicate primary vascular lesions. Nephron dissections revealed sacculations in distal tubules and collecting ducts of affected NE dogs. Renal disease did not develop in mongrel pups given injections of an homogenate or renal tissue from an affected NE dogs.