Adjuvant Effects of Low Doses of a Nuclease-Resistant Derivative of Polyinosinic Acid · Polycytidylic Acid on Antibody Responses of Monkeys to Inactivated Venezuelan Equine Encephalomyelitis Virus Vaccine

Abstract

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.