IgG binding characteristics of ferret Fcγ receptors.
Xiaoxuan Ge, Matthew Stoner, Joshua A Weiner, Melanee E Balderas Hernández, Noor Taher, Urjeet S Khanwalkar, Margaret C Carpenter, Jiwon Lee, Margaret E Ackerman
Abstract
Open AccessStudies in animal models are essential to expanding the scope of interventions evaluated for safety, immunogenicity, and efficacy in clinical trials. Ferrets (Mustela putorius furo) are a key small-animal model for examining acquisition, replication, transmission, and disease manifestation, with particular relevance in modeling diverse viruses that target the respiratory tract. However, despite use in studies of vaccine immunogenicity and protection, as well as passive antibody transfer, there is little data characterizing antibody and Fc receptor biology in this species. To address this gap, ferret Fcγ receptors (FcγRI, FcγRII, FcγRIII) were identified and recombinantly expressed and characterized for binding to recombinant ferret and human IgG. In general, ferret IgG bound each receptor with slightly higher affinity than the human IgG subclasses, which exhibited similar ferret receptor binding profiles as observed for human receptors (IgG1 and IgG3 > IgG4 > IgG2). N-linked glycosylation motifs on ferret receptors were typically occupied, and binding was dependent on IgG Fc glycosylation. While further insight into the expression patterns and activities of innate immune cells stimulated by IgG is still needed, these data define Fc - FcγR recognition patterns in ferrets to help support optimal clinical translation of passive and active immunization studies.