An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants
Publication date
2022-02-17
Authors
Du, Wenjuan
Hurdiss, Daniel L
Drabek, D.
Mykytyn, A. Z.
Kaiser, F.K.
Gonzalez-Hernandez, M.
Munoz-Santos, D.
Lamers, M. M.
van Haperen, R.
Li, W.
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Document Type
/dk/atira/pure/researchoutput/researchoutputtypes/workingpaper/preprint
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cc_by_nc_nd
Abstract
The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity.
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Citation
Du, W J, Hurdiss, D L, Drabek, D, Mykytyn, A Z, Kaiser, F K, Gonzalez-Hernandez, M, Munoz-Santos, D, Lamers, M M, van Haperen, R, Li, W T, Drulyte, I, Wang, C Y, Sola, I, Armando, F, Beythien, G, Ciurkiewicz, M, Baumgartner, W, Guilfoyle, K, Smits, T, van der Lee, J, van Kuppeveld, F J M, van Amerongen, G, Haagmans, B L, Enjuanes, L, Osterhaus, A D M E, Grosveld, F & Bosch, B 2022 'An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants' bioRxiv. https://doi.org/10.1101/2022.02.17.480751