Asunto(s)
Carboximetilcelulosa de Sodio/uso terapéutico , Inductores de Interferón/uso terapéutico , Neoplasias Laríngeas/tratamiento farmacológico , Metilcelulosa/análogos & derivados , Papiloma/tratamiento farmacológico , Péptidos/uso terapéutico , Poli I-C/uso terapéutico , Polilisina/uso terapéutico , Preescolar , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Papiloma/secundarioRESUMEN
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.
Asunto(s)
Adyuvantes Inmunológicos , Virus de la Encefalitis Equina Venezolana/inmunología , Poli I-C/inmunología , Animales , Anticuerpos Antivirales/biosíntesis , Formación de Anticuerpos , Haplorrinos , Interferones/biosíntesis , Macaca mulatta , Vacunas ViralesRESUMEN
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.