The neonatal Fc receptor (FcRn) is key to the ~3-week plasma half-life and transport of immunoglobulin G (IgG) across cellular barriers (transcytosis). Here we address the hypothesis that interaction of viral (SARS-CoV-2) antigen with anti-viral IgG affects transcytosis. We established an in vitro transwell assay system to study FcRn-mediated IgG transcytosis across a polarized epithelial cell barrier. Using sotrovimab, a human anti-SARS-CoV-2 neutralizing monoclonal IgG, we studied the impact of SARS-CoV-2 spike protein binding on transcytosis. Our results show decreased sotrovimab transcytosis upon immune complex formation. Recently, we detected and purified anti-SARS-CoV-2 IgG from intravenous immunoglobulin (IGIV) lots manufactured post-COVID. We evaluated SARS-CoV-2 spike protein binding to pre- and post-COVID IGIV lots using biolayer interferometry and ELISA, followed by in vitro measurements of IgG transcytosis. Our findings may help elucidate whether viral loads hamper anti-SARS-CoV-2 IgG transcytosis into the alveolar space, vital information needed to inform proper immunoglobulin product dosing.
Learning Objectives:
Upon completion, participants will be able to demonstrate knowledge of the importance of FcRn-mediated IgG transcytosis in establishing IgG half-life and the impact of SARS-CoV-2 binding on IgG transcytosis
