Biochemistry Commons^™

Structure-Guided Molecular Grafting Of A Complex Broadly Neutralizing Viral Epitope, G. Bajic, M. J. Maron, T. M. Caradonna, M. Tian, Adam Mermelstein , '21, Daniela Fera, G. Kelsoe, M. Kuraoka, A. G. Schmidt

Chemistry & Biochemistry Faculty Works

Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a “universal” influenza vaccine may come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use noncirculating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These “resurfaced” HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization, we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and …