Interferon Inducers against Infectious Diseases

Abstract

Abstract : The double-stranded polyribonucleotide, poly IC(polyinosinic- polycytidylic acid) is an interferon inducer. In primates it is not an effective antiviral agent, presumably because circulating nucleases quickly degrade it. When complexed with cationic poly L-lysine (PLL) and anionic carboxymethylcellulose (CMC) the resultant complex, poly ICLC, is effective in humans. However, CMC appears not to be excreted or metabolized, and may be a carcinogen. Our goal was to prepare effective, safe antiviral agents devoid of CMC, less toxic than poly ICLC, and non-immunogenic. To these ends, our efforts were to develop anionic polymers to replace CMC. We also replaced both PLL and CMC by modifying the PLL with engrafted polysaccharides. our research has resulted in the demonstration that effective IFN inducers can be formulated without using carboxymethylcellulose. Our new formulations have shown effective IFN induction and antiviral activity, some of them against two viruses, Rift Valley Fever and Punta Toro. Most of them are less toxic than Poly ICLC. Of 7 types of formulations tested for immunogenicity, were found to be non- immunogenic. The most promising candidates for large-scale development as antivirals are IC-(PLL-Dextran), and ICL-beta-cyclodextrin sulfate.... Interferon inducers, Antivirals, Ds RNA, Rift valley fever, Virus, Punta Toro virus, Banzi virus.