Pharmacokinetics study of a novel chimeric single-chain variable fragment antibody against western equine encephalitis virus

A novel recombinant single-chain fragment variable (scFv) antibody against western equine encephalitis (WEE) virus has been previously constructed and partially characterized. The RS10B5huFc antibody was made by fusing an ant i-WEE scFv to a human heavy-chain IgG(1) constant region. The RS10B5huFc an tibody was functional in binding to WEE virus in enzyme-linked immunosorben t assays (ELISAs), and the Fc domain of the antibody was capable of effecto r functions, such as binding to protein G and human complement. In this stu dy, the RS10B5huFc antibody was further characterized by BIAcore analyses a nd was found to possess a binding affinity to a WEE virus epitope (K[D] = 9 .14 x 10(-6) M), 4.5-fold lower than its parental mouse monoclonal antibody (MAb) 10B5 E7E2 (K[D] = 2 x 10(-6) M). No cross-reactivity was found betwe en the RS10B5huFc antibody and three other alphaviruses (Sindbis virus [SIN ], Venezuelan equine encephalitis [VEE] virus, and eastern equine encephali tis [EEE] virus). Pharmacokinetics studies showed that the RS10B5huFc antib ody (free and encapsulated) was found to be retained in the lungs of mice f or greater than 48 h when administered intranasally, In contrast, when admi nistered intramuscularly to mice, the RS10B5huFc antibody was not detected in the lungs and only found in the liver and kidneys.