8di5

Publication Abstract from PubMed

The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human V(H) domain, F6, which we generated by sequentially panning large phage-displayed V(H) libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region. Attachment of an Fc region to a fusion of F6 and ab8, a previously characterized V(H) domain, resulted in a construct (F6-ab8-Fc) that broadly and potently neutralized VOCs including Omicron. Additionally, prophylactic treatment using F6-ab8-Fc reduced live Beta (B.1.351) variant viral titers in the lungs of a mouse model. Our results provide a new potential therapeutic against SARS-CoV-2 variants including Omicron and highlight a vulnerable epitope within the spike that may be exploited to achieve broad protection against circulating variants.

Potent and broad neutralization of SARS-CoV-2 variants of concern (VOCs) including omicron sub-lineages BA.1 and BA.2 by biparatopic human VH domains.,Chen C, Saville JW, Marti MM, Schafer A, Cheng MH, Mannar D, Zhu X, Berezuk AM, Banerjee A, Sobolewski MD, Kim A, Treat BR, Da Silva Castanha PM, Enick N, McCormick KD, Liu X, Adams C, Hines MG, Sun Z, Chen W, Jacobs JL, Barratt-Boyes SM, Mellors JW, Baric RS, Bahar I, Dimitrov DS, Subramaniam S, Martinez DR, Li W iScience. 2022 Aug 19;25(8):104798. doi: 10.1016/j.isci.2022.104798. Epub 2022 , Jul 20. PMID:35875685^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.