Mucosal nanobody IgA as inhalable and affordable prophylactic and therapeutic treatment against SARS-CoV-2 and emerging variants

• DOI: 10.3389/fimmu.2022.995412
• Publication Date: 2022-09-12T04:25:06Z
• Authors: Qi Li; Fiachra Humphries; Roxie C. Girardin; Aaron Wallace; Monir Ejemel; Alla Amcheslavsky; Conor T. McMahon; Zachary A. Schiller; Zepei Ma; John Cruz; Alan P. Dupuis; Anne F. Payne; Arooma Maryam; Nese Kurt Yilmaz; Kathleen A. McDon...; Brian G. Pierce; Celia A. Schiffer; Andrew C. Kruse; Mark S. Klempner; Lisa A. Cavacini; Katherine A. Fitz...; Yang Wang
• Keywords: Single-domain antibody

Anti-COVID antibody therapeutics have been developed but not widely used due to their high cost and escape of neutralization from the emerging variants. Here, we describe development VHH-IgA1.1, a nanobody IgA fusion molecule as an inhalable, affordable less invasive prophylactic therapeutic treatment against SARS-CoV-2 Omicron VHH-IgA1.1 recognizes conserved epitope spike protein Receptor Binding Domain (RBD) potently neutralizes major global variants concern (VOC) including variant its sub lineages BA.1.1, BA.2 BA.2.12.1. is also much more potent compared IgG Fc construct, demonstrating importance mediated mucosal protection for infection. Intranasal administration prior or after challenge conferred significant severe respiratory disease in K18-ACE2 transgenic mice infected with VOC. More importantly, cost-effective production, produced Pichia pastoris had comparable potency mammalian antibodies. Our study demonstrates that intranasal affordably VHH-IgA provides effective immunity infection