Effect of FcRn on in vivo pharmacokinetics of a novel monoclonal antibody against West Nile virus MIL94 / 中国药理学通报

ABSTRACT

Aim To investigate the effects of different species Fc receptors (FcRn) on pharmacokinetic characteristics of MIL94, a monoclonal antibody against West Nile virus developed by Academy of Military Sciences, which has a neutralizing effect on West Nile virus and whose maintenance time in vivo is closely related to its antiviral effect. Methods The pharmacokinetic characteristics of MIL94 in mice expressing FcRn of different species (wild-type mice, hFcRn mice and FcRn knockout mice) were compared-. Wild-type mice and FcRn knockout mice were injected intravenously with MIL94 respectively. HFcRn mice were randomly divided into four groups. Two groups were injected intravenously with MIL94, and the other two groups were injected intravenously with intravenous immunoglobulin (IVIG) and then intravenously with MIL94. Indirect ELISA was used to determine the MIL94 concentration in mouse serum. WinNonlin software was used to calculate the pharmacokinetic parameters. Results After intravenous injection with MIL94, the in vivo pharmacokinetics were basically linear. The distribution volume of MIL94 in animals was related to FcRn. The half-life in vivo varied greatly between different groups. Conclusions FcRn can affect the half-life of MIL94 in different species mainly via alternation of its elimination and distribution. It is expected that the half-life of FcRn in human will be longer than that in preclinical animals.