Structural insights for neutralization of Omicron variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody

In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)–specific m...

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Published inScience advances Vol. 8; no. 40; p. eadd2032
Main Authors Kumar, Sanjeev, Patel, Anamika, Lai, Lilin, Chakravarthy, Chennareddy, Valanparambil, Rajesh, Reddy, Elluri Seetharami, Gottimukkala, Kamalvishnu, Davis-Gardner, Meredith E., Edara, Venkata Viswanadh, Linderman, Susanne, Nayak, Kaustuv, Dixit, Kritika, Sharma, Pragati, Bajpai, Prashant, Singh, Vanshika, Frank, Filipp, Cheedarla, Narayanaiah, Verkerke, Hans P., Neish, Andrew S., Roback, John D., Mantus, Grace, Goel, Pawan Kumar, Rahi, Manju, Davis, Carl W., Wrammert, Jens, Godbole, Sucheta, Henry, Amy R., Douek, Daniel C., Suthar, Mehul S., Ahmed, Rafi, Ortlund, Eric, Sharma, Amit, Murali-Krishna, Kaja, Chandele, Anmol
Format Journal Article
LanguageEnglish
Published United States American Association for the Advancement of Science 07.10.2022
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Abstract In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)–specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC 50 ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages. A rare human monoclonal antibody neutralizes all SARS-CoV-2 Omicron variants by targeting a conserved epitope on the RBD.
AbstractList In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19-recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)-specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC50 ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19-recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)-specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC50 ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.
In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)–specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC 50 ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages. A rare human monoclonal antibody neutralizes all SARS-CoV-2 Omicron variants by targeting a conserved epitope on the RBD.
In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19-recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)-specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.
Author Edara, Venkata Viswanadh
Douek, Daniel C.
Godbole, Sucheta
Henry, Amy R.
Suthar, Mehul S.
Chandele, Anmol
Sharma, Amit
Lai, Lilin
Kumar, Sanjeev
Davis, Carl W.
Patel, Anamika
Neish, Andrew S.
Valanparambil, Rajesh
Linderman, Susanne
Nayak, Kaustuv
Rahi, Manju
Wrammert, Jens
Dixit, Kritika
Roback, John D.
Davis-Gardner, Meredith E.
Goel, Pawan Kumar
Cheedarla, Narayanaiah
Ahmed, Rafi
Murali-Krishna, Kaja
Singh, Vanshika
Verkerke, Hans P.
Chakravarthy, Chennareddy
Gottimukkala, Kamalvishnu
Frank, Filipp
Mantus, Grace
Bajpai, Prashant
Ortlund, Eric
Sharma, Pragati
Reddy, Elluri Seetharami
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  surname: Linderman
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These authors contributed equally to this work.
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Snippet In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who...
In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19-recovered individuals in India who...
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SubjectTerms Angiotensin-Converting Enzyme 2
Antibodies, Monoclonal - chemistry
Antibodies, Viral
Biomedicine and Life Sciences
Coronavirus
COVID-19
Epitopes
Humans
Neutralization Tests
SARS-CoV-2 - genetics
SciAdv r-articles
Spike Glycoprotein, Coronavirus
Title Structural insights for neutralization of Omicron variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody
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