Assuntos
Adjuvantes Imunológicos/imunologia , Benzofuranos/imunologia , Encefalomielite Equina/microbiologia , Encefalomielite Equina Venezuelana/microbiologia , Fluorenos/imunologia , Tilorona/imunologia , Vacinas Atenuadas/imunologia , Animais , Anticorpos Antivirais/análise , Formação de Anticorpos , Feminino , Formaldeído , Macaca mulatta , Masculino , CamundongosRESUMO
Polyriboinosinic.polyribocytidylic acid [poly(I).poly(C)] stabilized with poly-l-lysine and carboxymethylcellulose [poly(ICLC)] has been previously shown to be a compound with marked adjuvant activity when given in high doses with inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine. This study investigated the effects of much lower doses of poly(ICLC) on the magnitude and kinetics of the primary and secondary humoral antibody responses of rhesus monkeys to inactivated VEE virus vaccine. Monkeys given a single injection of vaccine developed very low neutralizing antibody titers, whereas those given adjuvant plus vaccine had 30- to 100-fold-higher titers which remained elevated for longer than 6 months. Low doses of poly(ICLC) given with VEE virus vaccine resulted in a profound but transient increase in priming of secondary antibody responses to the antigen. In contrast, the administration of poly-l-lysine and carboxymethylcellulose alone without the poly(I).poly(C) component of the complex had no adjuvant effect on antibody responses of monkeys to VEE virus vaccine. The temporal development of antibody by class (immunoglobulin M-immunoglobulin G) in monkeys given two injections of adjuvant-vaccine was not different from that with vaccine alone. Serial hematological and clinical chemistry determinations on monkeys given single or multiple doses of poly(ICLC) with vaccine were not different from values in monkeys given vaccine alone.
Assuntos
Adjuvantes Imunológicos , Vírus da Encefalite Equina Venezuelana/imunologia , Poli I-C/imunologia , Animais , Anticorpos Antivirais/biossíntese , Formação de Anticorpos , Haplorrinos , Interferons/biossíntese , Macaca mulatta , Vacinas ViraisRESUMO
Polyriboinosinic-polyribocytidylic acid, stabilized with poly-L-lysine and carboxymethylcellulose (poly ICLC), favorably alters the pathogenesis of Venezuelan equine encephalomyelitis virus infection in rhesus monkeys by decreasing the number of infected monkey that become detectably viremic and by delaying the onset of viremia in the remaining monkeys. Poly ICLC is known to induce high circulating levels of interferon in primates, and the interferon system is assumed to be the mechanism by which poly ICLC exerts its antiviral effect. Poly ICLC treatment was associated with a few deaths, but only under certain conditions of infection and handling. The death of some infected, treated monkeys in the absence of death in monkeys that were either infected and untreated or treated and uninfected suggests a synergistic toxicity resulting from the combination of infection, handling, and poly ICLC treatment, although other explanations are possible.
Assuntos
Vírus da Encefalite Equina Venezuelana/efeitos dos fármacos , Poli I-C/farmacologia , Animais , Carboximetilcelulose Sódica , Vírus da Encefalite Equina Venezuelana/patogenicidade , Encefalomielite Equina Venezuelana , Feminino , Haplorrinos , Interferons/biossíntese , Macaca mulatta , Masculino , PolilisinaRESUMO
Experimental infection of rhesus monkeys (Macaca mulatta) with Machupo virus produced a hemorrhagic disease similar to that of Bolivian hemorrhagic fever in humans. The disease in infected animals was also characterized by the development of hypotension and coagulation abnormalities as indicated by severe thrombocytopenia and prolongation of the activated partial thromboplastin time. Evidence for disseminated intravascular coagulation was inconclusive due to the presence of normal to elevated fibrinogen levels, relatively low levels of circulating fibrin split products, and the lack of widespread fibrin thrombus deposition. The most likely causes of the hemorrhagic tendencies of this disease in infected monkeys were thrombocytopenia and decreased synthesis of coagulation and other plasma proteins due to severe hepatocellular necrosis. Hypotension may also have been due to decreased plasma protein synthesis.
Assuntos
Febre Hemorrágica Americana/diagnóstico , Animais , Pressão Sanguínea , Feminino , Haplorrinos , Febre Hemorrágica Americana/patologia , Febre Hemorrágica Americana/fisiopatologia , Hemostasia , Macaca mulatta , MasculinoRESUMO
A highly virulent strain of Venezuelan equine encephalomyelitis (VEE) virus produced less severe histopathologic changes in brain tissues of mice previously exposed to sublethal total-body x-irradiation than it caused in nonirradiated mice. Prior exposure to 600 R of x-irradiation virtually eliminated the lesions of vasculitis and encephalitis that were found in the infected nonirradiated control mice. Mean peak brain lesion scores generally decreased as radiation exposure dose was increased. Irradiation of mice before inoculation often decreased median time to death, whereas the severity of pathologic changes in brain tissues from inoculated irradiated mice was often reduced, without significantly altering ultimate host survival. The inflammatory response did not appear to have a significant role in clearance of this virus from the brain. There was no evidence that participation of the immune response contributed to total mortality from VEE virus encephalitis, as indicated by the failure of radiation immunosuppression to reduce mortality. Death apparently was caused by the direct cytocidal effects of VEE virus replication.
Assuntos
Formação de Anticorpos/efeitos da radiação , Encefalomielite Equina/patologia , Encefalomielite Equina Venezuelana/patologia , Animais , Sangue/microbiologia , Encéfalo/microbiologia , Encéfalo/patologia , Vírus da Encefalite Equina Venezuelana/isolamento & purificação , Encefalomielite Equina Venezuelana/imunologia , Encefalomielite Equina Venezuelana/microbiologia , Terapia de Imunossupressão , Masculino , CamundongosRESUMO
The epizootic Trinidad donkey strain of Venezuelan equime encephalomyelitis virus (VEE) was cleared slowly from the circulation of rhesus monkeys following intravenous inoculation, while the live, attenuated vaccine strain, TC-83, was cleared rapidly. The efficent clearance of TC-83 vaccine may be a factor in the lower viremia and benign course of TC-83 virus infection in rhesus monkeys.