Pre-clinical safety evaluation for mRNA-vaccine development in mouse model

ABSTRACT

Messenger RNA (mRNA) vaccine has emerged as an attractive agent for prevention of infectious disease and anti-cancer therapy. However, there is a fatal risk that the safety evaluation for mRNA vaccine have not been fully studied yet. In this study, we evaluated the safety of four type of COVID-19 S-protein targeting mRNA vaccines with different compositions (C2/ LNP90, C2LNP128, C3LNP90 and C3LNP128). Theses vaccines were intramuscularly injected to 6-wk old male and female ICR mice with twice at an interval of 2 wks. The necropsy was carried out on 2 days or 14 days after secondary injection. The results showed that the body weight was decreased for 2days after the first injection in C2/LNP128 and C3/LNP128-injected mice, but it was almost recovered at 7day post injection (dpi). At 2 dpi after secondary injection, the endpoint blood analysis of demonstrated that C2/LNP128 and C3/LNP128 decreased the number of lymphocytes, monocytes and reticulocytes carrying the abnormal level of liver function indicator such as albumin, AST, ALT and total protein. Additionally, C2/LNP128 decreased the number of platelet and C3LNP128 decreased the number of red blood cells, respectably. Spleen and inguinal lymph node were enlarged in all experimental group. Notably, C2/LNP128 and C3/LNP128 induced severe edema in injection site, femoris muscle. At 14 dpi after secondary injection, the toxicity that was observed at 2 dpi after secondary injection was recovered. These results suggest that the potential side effects of mRNA vaccines must be systematically evaluated with multiple aspect of toxicology.