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 anti-WEE scFv to a human heavy-chain IgG1 constant region. The RS10B5huFc antibody was functional in binding to WEE virus in enzyme-linked immunosorbent assays (ELISAs), and the Fc domain of the antibody was capable of effector functions, such as binding to protein G and human complement. In this study, the RS10B5huFc antibody was further characterized by BIAcore analyses and 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 between the RS10B5huFc antibody and three other alphaviruses (Sindbis virus [SIN], Venezuelan equine encephalitis [VEE] virus, and eastern equine encephalitis [EEE] virus). Pharmacokinetics studies showed that the RS10B5huFc antibody (free and encapsulated) was found to be retained in the lungs of mice for greater than 48 h when administered intranasally. In contrast, when administered intramuscularly to mice, the RS10B5huFc antibody was not detected in the lungs and only found in the liver and kidneys.
Long
M C
MC
Chemical and Biological Defence Section, Defence Research Establishment Suffield, Medicine Hat, Alberta, Canada.
Marshall
K E
KE
Kearney
B J
BJ
Ludwig
G V
GV
Wong
J P
JP
Nagata
L P
LP
D000281:Administration, Intranasal; D000524:Alphavirus / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D000918:Antibody Specificity; D003429:Cross Reactions; D004339:Drug Compounding; D004667:Encephalitis Virus, Western Equine / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007273:Injections, Intramuscular; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000914:Antibodies, Viral; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D008081:Liposomes; D011993:Recombinant Fusion Proteins