Variations in the contribution of induced interferon and adjuvanticity to the antiviral effect of different polyinosinic acid . polycytidylic acid formulations in mice infected with encephalomyocarditis virus

Treatment of mice with polyinosinic acid . polycytidylic acid [poly(I) . poly(C)] 6 h before infection and once daily on days 1, 2, 3, 4, 7, and 10 after infection with encephalomyocarditis virus was found to confer no additional protection as compared with a single treatment 6 h before infection. When complexed with a colloid formed between carboxymethylcellulose and polylysine, poly(I) . poly(C) conferred significant additional protection with the multiple treatment regimen compared with a single treatment of 6 h before infection. The additional antiviral activity of multiple treatments could not be entirely attributed to interferon induction by the complexed form of poly(I) . poly(C), because free and complexed poly(I) . poly(C) both caused hyporesponsiveness to interferon induction after multiple treatments. However, mice protected against encephalomyocarditis virus infection by multiple treatments with the colloidal complex form of poly(I) . poly(C) showed a significant increase in resistance to reinfection, and this was attributable to adjuvant effects of the colloidal complex form of poly(I) . poly(C). The contribution of interferon induction and adjuvanticity of the poly(I) . poly(C) formulations varied with the times of treatment relative to infection, the dose of polynucleotide material, and the virus dose.