Engineering recombinant ferret IgA against influenza viruses and coronaviruses for reagent validation and musocal immunity assessment 4743

Abstract Description Despite the global influenza vaccination program, influenza A and B virus infections continue to cause significant disease and economic burdens due to strain mismatch reducing vaccine efficacy in at-risk populations. Novel vaccination strategies are under development, but mucosal immunity, which has been shown to offer increased breadth of protection, is understudied, in part due to challenges in measuring mucosal immune responses. Ferrets are the gold-standard animal model for influenza infection, yet the field lacks reagents to assess mucosal immunity. To address this gap, we have engineered recombinant ferret monomeric, dimeric, and secretory IgA containing the binding fragment (Fab) region of the pan-hemagglutinin (HA) monoclonal antibody (mAb), CR9114 to enable measurement of ferret mucosal immune responses and define the role of mucosal immunity. The aim of this study is twofold: to provide reagents for robust mucosal assessment in ferrets and validate the functionality and efficacy of the IgA constructs. Thus far, we have confirmed robust affinity of all IgA constructs to their respective antigens and comparable HA inhibition of CR9114 IgA. Other functional assays are ongoing, including viral neutralization and transcytosis, as well as treatment studies in ferrets, where we will measure the protection from viral challenge. Structural assessment of dimeric IgA is underway to elucidate the undiscovered structure of ferret IgA in complex with the respective antigens. Funding Sources NIH Options 11 “Recombinant ferret pan-influenza HA and pan-coronavirus spike IgG and IgA reagents for improved serological and mucosal antibody assessment and mechanistic studies”. (Award number currently in development). Topic Categories Mucosal and Regional Immunology (MUC)