Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein

Abstract The CR3022 antibody, selected from a group of SARS-CoV monoclonal antibodies for its ability to cross-react with SARS-CoV-2, has been examined for its ability to bind to the ectodomain of the SARS-CoV-2 spike glycoprotein. Using cryo-electron microscopy we show that antibody binding requires rearrangements in the S1 domain that result in dissociation of the spike.

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Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529

10.1101/2021.12.27.474307 ◽

2021 ◽

Author(s):

Tongqing Zhou ◽

Lingshu Wang ◽

John Misasi ◽

Amarendra Pegu ◽

Yi Zhang ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Structural Basis ◽

Resistance Mutations ◽

Binding Surface ◽

New Variant ◽

Rapid Spread ◽

Structural Mechanisms ◽

The Impact ◽

Insight Into ◽

Potent Neutralization

With B.1.1.529 SARS-CoV-2 variant's rapid spread and substantially increased resistance to neutralization by vaccinee and convalescent sera, monoclonal antibodies with potent neutralization are eagerly sought. To provide insight into effective neutralization, we determined cryo-EM structures and evaluated potent receptor-binding domain (RBD) antibodies for their ability to bind and neutralize this new variant. B.1.1.529 RBD mutations altered 16% of the RBD surface, clustering on a ridge of this domain proximal to the ACE2-binding surface and reducing binding of most antibodies. Significant inhibitory activity was retained, however, by select monoclonal antibodies including A19-58.1, B1-182.1, COV2-2196, S2E12, A19-46.1, S309 and LY-CoV1404, which accommodated these changes and neutralized B.1.1.529 with IC50s between 5.1-281 ng/ml, and we identified combinations of antibodies with potent synergistic neutralization. Structure-function analyses delineated the impact of resistance mutations and revealed structural mechanisms for maintenance of potent neutralization against emerging variants.

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Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

Emerging Microbes & Infections ◽

10.1080/22221751.2019.1597644 ◽

2019 ◽

Vol 8 (1) ◽

pp. 516-530 ◽

Cited By ~ 48

Author(s):

Ivy Widjaja ◽

Chunyan Wang ◽

Rien van Haperen ◽

Javier Gutiérrez-Álvarez ◽

Brenda van Dieren ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Spike Glycoprotein ◽

Human Monoclonal Antibodies

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Faculty Opinions recommendation of An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1019537.242488 ◽

2004 ◽

Author(s):

Peter Openshaw

Keyword(s):

Monoclonal Antibodies ◽

B Cells ◽

Efficient Method ◽

Memory B Cells ◽

Sars Coronavirus ◽

Human Monoclonal Antibodies ◽

Potent Neutralization

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Development of Whole-Porcine Monoclonal Antibodies with Potent Neutralization Activity against Classical Swine Fever Virus from Single B Cells

ACS Synthetic Biology ◽

10.1021/acssynbio.8b00365 ◽

2019 ◽

Vol 8 (5) ◽

pp. 989-1000

Author(s):

Haisi Dong ◽

Ang Su ◽

Dongmei Lv ◽

Lerong Ma ◽

Jianwei Dong ◽

...

Keyword(s):

Monoclonal Antibodies ◽

B Cells ◽

Classical Swine Fever Virus ◽

Classical Swine Fever ◽

Fever Virus ◽

Neutralization Activity ◽

Potent Neutralization

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Comparison of bovine coronavirus (BCV) antigens: Monoclonal antibodies to the spike glycoprotein distinguish between vaccine and wild-type strains

Virology ◽

10.1016/0042-6822(91)90163-6 ◽

1991 ◽

Vol 183 (1) ◽

pp. 442-445 ◽

Cited By ~ 19

Author(s):

Khalid A. Hussain ◽

Johannes Storz ◽

Konstantin G. Kousoulas

Keyword(s):

Monoclonal Antibodies ◽

Wild Type ◽

Spike Glycoprotein ◽

Bovine Coronavirus ◽

Type Strains

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Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19

Vaccines ◽

10.3390/vaccines9030296 ◽

2021 ◽

Vol 9 (3) ◽

pp. 296

Author(s):

Jiao Tong ◽

Chenxi Zhu ◽

Hanyu Lai ◽

Chunchao Feng ◽

Dapeng Zhou

Keyword(s):

Monoclonal Antibodies ◽

Vaccine Candidate ◽

Spike Protein ◽

Heptad Repeat ◽

Peptide Array ◽

Receptor Binding Domain ◽

Protein Vaccine ◽

Direct Binding ◽

Linear Epitopes ◽

Potent Neutralization

The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0–7–14 day schedule. The results showed that a Spike protein-specific antibody was induced at Day 21 with titer of above 50,000 on average, as measured by direct binding. The neutralizing titer was above 1000 on average, as determined by a pseudo-virus using monoclonal antibodies (40592-MM57 and 40591-MM43) with IC50 at 1 μg/mL as standards. The protein/peptide array-identified receptor-binding domain (RBD) was considered as immunodominant. No linear epitopes were found in the RBD, although several linear epitopes were found in the C-terminal domain right after the RBD and heptad repeat regions. Our study supports the efficacy of a recombinant trimeric Spike protein vaccine candidate for COVID-19 that is safe and ready for storage and distribution in developing countries.

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