Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus

To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to prev...

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Published in:eLife Vol. 12
Main Authors: Ketaren, Natalia E, Mast, Fred D, Fridy, Peter C, Olivier, Jean Paul, Sanyal, Tanmoy, Sali, Andrej, Chait, Brian T, Rout, Michael P, Aitchison, John D
Format: Journal Article
Language:English
Published: England eLife Science Publications, Ltd 07-05-2024
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Abstract To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single-domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here, we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast et al., 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.
AbstractList To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single-domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here, we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast et al., 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.
Audience Academic
Author Olivier, Jean Paul
Mast, Fred D
Chait, Brian T
Sanyal, Tanmoy
Aitchison, John D
Fridy, Peter C
Ketaren, Natalia E
Sali, Andrej
Rout, Michael P
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  organization: Department of Biochemistry, University of Washington, Seattle, United States
BackLink https://www.ncbi.nlm.nih.gov/pubmed/38712823$$D View this record in MEDLINE/PubMed
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Keywords viruses
nanobodies
chemical biology
infectious disease
neutralization
betacoronavirus
biochemistry
SARS-CoV-2 variants
microbiology
single-domain antibodies
human
spike
Language English
License 2023, Ketaren, Mast, Fridy et al.
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These authors contributed equally to this work.
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Snippet To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As...
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SubjectTerms Animals
Antibodies
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Antibodies, Viral - therapeutic use
betacoronavirus
Biochemistry and Chemical Biology
COVID-19
COVID-19 - immunology
COVID-19 - virology
Enzymes
FDA approval
Health aspects
Humans
Immune response
Immunotherapy
Infections
Infectious diseases
Microbiology and Infectious Disease
Monoclonal antibodies
Mutation
Nanobodies
neutralization
Proteins
Research Advance
SARS-CoV-2 - immunology
SARS-CoV-2 variants
Severe acute respiratory syndrome coronavirus 2
single-domain antibodies
Single-Domain Antibodies - immunology
spike
Spike Glycoprotein, Coronavirus - immunology
Spike protein
Vaccination
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Title Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus
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