Evaluation of the safety profile of ssRNA adjuvant derived from the IGR IRES region of CrPV

Abstract

Abstract Adjuvants enhance the efficacy of vaccines by stimulating immune response relate gene expression and pathways. However, development of an appropriate adjuvant for a specific vaccine type is difficult, because of their unwanted systemic and local adverse effects. Despite intensive efforts for more than 80 years, there are only a few approved adjuvants. Poly I:C, a double stranded RNA was experimentally used as an adjuvant since 1970s. Although poly I:C dramatically stimulates the innate immune response, which is a prerequisite of a good adjuvant, inducing effective immune response while avoiding adverse events is a major challenge. In this study, we evaluated the safety and toxicological profile of a high-dose (200ug/mouse) single stranded RNA (ssRNA) derived from the intergenic region (IGR) internal ribosome entry site (IRES) of cricket paralysis virus (CrPV) as a novel adjuvant in a mouse model. The results indicate that there were no significant differences in body weight and food intake pattern in mice immunized with ssRNA adjuvant and the control group. Hematological parameters like ALT and AST levels appeared to be normal in both treated and control group. Histology of organs such as liver, spleen, lung, and kidney appeared to be normal. There was no evidence of tissue damage in mice treated with ssRNA adjuvant and control group. IgE levels, which is marker of autoimmune disease, is also not different compared with treated group and control group. In addition, the adjuvant effect is similar in both high-dose and low-dose (20ug/mouse) treated groups. In conclusion, novel ssRNA adjuvant exhibited a safe toxicological profile in mouse model. The results obtained may be utilized for conducting further clinical trials in humans.