Author:
Li Qi,Humphries Fiachra,Girardin Roxie C.,Wallace Aaron,Ejemel Monir,Amcheslavsky Alla,McMahon Conor T.,Schiller Zachary A.,Ma Zepei,Cruz John,Dupuis Alan P.,Payne Anne F.,Maryam Arooma,Yilmaz Nese Kurt,McDonough Kathleen A.,Pierce Brian G.,Schiffer Celia A.,Kruse Andrew C.,Klempner Mark S.,Cavacini Lisa A.,Fitzgerald Katherine A.,Wang Yang
Abstract
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 the development of VHH-IgA1.1, a nanobody IgA fusion molecule as an inhalable, affordable and less invasive prophylactic and therapeutic treatment against SARS-CoV-2 Omicron variants. VHH-IgA1.1 recognizes a conserved epitope of SARS-CoV-2 spike protein Receptor Binding Domain (RBD) and potently neutralizes major global SARS-CoV-2 variants of concern (VOC) including the Omicron variant and its sub lineages BA.1.1, BA.2 and BA.2.12.1. VHH-IgA1.1 is also much more potent against Omicron variants as compared to an IgG Fc fusion construct, demonstrating the importance of IgA mediated mucosal protection for Omicron infection. Intranasal administration of VHH-IgA1.1 prior to or after challenge conferred significant protection from severe respiratory disease in K18-ACE2 transgenic mice infected with SARS-CoV-2 VOC. More importantly, for cost-effective production, VHH-IgA1.1 produced in Pichia pastoris had comparable potency to mammalian produced antibodies. Our study demonstrates that intranasal administration of affordably produced VHH-IgA fusion protein provides effective mucosal immunity against infection of SARS-CoV-2 including emerging variants.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Subject
Immunology,Immunology and Allergy
Cited by
5 articles.
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