Emig, C. J. | bioRxiv Science

bioRxiv2024

CXADR is a Human IgG Fc Receptor

CXADR is a membrane protein present in epithelial tight junctions and other tissues with a variety of known functions, in addition to its role as entry receptor for coxsackie B virus and adenovirus 2 and 5. We identified a previously unknown function of CXADR as a binding partner for human IgG but not IgA, IgE, IgM, or ScFv in a non paratope specific manner. Binding was specific to human and rabbit IgG, and not observed for mouse, rat, donkey, or goat IgG. Binding of Ig to CXADR is inhibited by FcBlock (BD), and is competitive with anti-Fc binding secondary antibodies, but not anti-Fab secondary antibodies, indicating that CXADR binds the Fc portion of IgG. CXADR, being a member of the immune superfamily of proteins, has similar structural homology to other Ig binding proteins, including Fc receptors. We conclude that CXADR has a previously unknown function as a human Fc receptor, serving as a direct link between the humoral adaptive immune system and many cell types in the human body previously unknown to express FcR.

immunology↗

bioRxiv2021

AUG-3387, a Human-Derived Monoclonal Antibody Neutralizes SARS-CoV-2 Variants and Reduces Viral Load from Therapeutic Treatment of Hamsters In Vivo

Infections from the SARS-CoV-2 virus have killed over 4.6 million people since it began spreading through human populations in late 2019. In order to develop a therapeutic or prophylactic antibody to help mitigate the effects of the pandemic, a human monoclonal antibody (mAb) that binds to the SARS-CoV-2 spike protein was isolated from a convalescent patient following recovery from COVID-19 disease. This mAb, designated AUG-3387, demonstrates a high affinity for the spike protein of the original viral strains and all variants tested to date. In vitro pseudovirus neutralization and SARS-CoV-2 neutralization activity has been demonstrated in vitro. In addition, a dry powder formulation has been prepared using a Thin-Film Freezing (TFF) process that exhibited a fine particle fraction (FPF) of 50.95 {+/-} 7.69% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 3.74 {+/-} 0.73 {micro}m and 2.73 {+/-} 0.20, respectively. The dry powder is suitable for delivery directly to the lungs of infected patients using a dry powder inhaler device. Importantly, AUG-3387, administered as a liquid by intraperitoneal injection or the dry powder formulation delivered intratracheally into Syrian hamsters 24 hours after intranasal SARS-CoV-2 infection, demonstrated a dose-dependent reduction in the lung viral load of the virus. These data suggest that AUG-3387 formulated as a dry powder demonstrates potential to treat COVID-19.

pharmacology and toxicology↗