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.

Serological response to trivalent inactivated influenza vaccine in HIV-infected adults in Singapore

“…Immunogenicity of vaccine preparations can be improved by incorporating various Toll-like receptor (TLR) ligands into the formulations. [20][21][22][23][24] The production of pro-inflammatory cytokines is thought to be one of the main mechanisms for the enhancement effect. Pro-inflammatory cytokines, such as IL-12, is able to enhance CD4 C T cell functions 25,26 and bias toward Th1 responses.…”

Comparison of effects of adjuvants on efficacy of virion envelope herpes simplex virus vaccine against labial infection of BALB/c mice

“…The finding that the smaller polymer, MVE-2, was only partially effective is in keeping with previously reported size specificity (19). PICLC has proven to be an excellent adjuvant in conjunction with a number of weak vaccines, including Venezuelan equine encepha-litis, swine influenza, Japanese encephalitis, Rift Valley fever viruses, Hemophilus influenzae (8,18,28), and the herpes envelope vaccine used in these studies (9). It is not universally effective, however, since it was shown to decrease the response to pneumococcal polysaccharide antigen (18).…”

Broad-Spectrum Drugs Against Viral Agents

“…Poly (ICLC) adjuvant activity has been shown when co-administered with retinoic acid [ 58 ], VEEV vaccine [ 59 , 60 ] and the antimalarial drug chloroquine [ 61 ]. Synergism of poly (ICLC) with various anti-HIV compounds including cytokines (rIFN-α A, rIFN-β Ser 17, and rIFN-γ), reverse transcriptase inhibitors (azidothymidine and phosphonoformate (Foscarnet)), mRNA capping inhibitors (ribavirin), lipophile (amphotericin B) and glucosidase inhibitor (castanospermine) was observed [ 62 ].…”