ArticleProceedings of the National Academy of Sciences of the United States of America2023
The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Class switched bovine ultralong CDR H3 amplicons versus canonical in immune and non-immune tissues.Immunogenetics · 2026Article
- Therapeutic efficacy of bovine ultra-long CDR H3 antibody against BVDV in challenged BALB/c mouse model.Frontiers in immunology · 2026Article
- VNpj viruses · 2025Article
- Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025Article
- Comparative Molecular Dynamics Study of 19 Bovine Antibodies with Ultralong CDR H3.Antibodies (Basel, Switzerland) · 2025Article
- An ultra-long heavy chain bovine antibody neutralizes SARS-CoV-2 and reacts broadly with sarbecoviruses.bioRxiv : the preprint server for biology · 2025Article
- Stability convergence in natural antibodies with ultra-long hypervariable loops.Communications biology · 2025Article
- Facilitating and restraining virus infection using cell-attachable soluble viral receptors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms.Immunological reviews · 2024Review
- Investigating the IgM and IgG B Cell Receptor Repertoires and Expression of Ultralong Complementarity Determining Region 3 in Colostrum and Blood from Holstein-Friesian Cows at Calving.Animals : an open access journal from MDPI · 2024Article
- Post-translational modifications in the Protein Data Bank.Acta crystallographica. Section D, Structural biology · 2024Review
- Estimates of Sequences with Ultralong and Short CDR3s in the Bovine IgM B Cell Receptor Repertoire Using the Long-read Oxford Nanopore MinION Platform.ImmunoHorizons · 2024Article
- Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.PLoS pathogens · 2024Article
- The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies.Acta crystallographica. Section F, Structural biology communications · 2024Article
- HIV envelope trimers and gp120 as immunogens to induce broadly neutralizing antibodies in cows.bioRxiv : the preprint server for biology · 2024Article
- Modular design of bi- and multi-specific knob domain fusions.Frontiers in immunology · 2024Article
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Authors and funding
36 authors at 5 institutions in 1 country.
Ruiqi HuangApplied Biomedical Science Institute, San Diego, CA 92127.ORCID 0000-0001-5387-3428
Gabrielle Warner JenkinsApplied Biomedical Science Institute, San Diego, CA 92127.ORCID 0000-0002-2306-5128
Yunjeong KimCollege of Veterinary Medicine, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506.ORCID 0000-0002-2977-4400
Robyn L StanfieldDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-9521-9184
Amrinder SinghDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
Maria Martinez-YamoutDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0003-4376-437X
Gerard J KroonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-8038-7476
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0003-0137-8497
Abigail M JacksonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.
Abigail KelleyApplied Biomedical Science Institute, San Diego, CA 92127.
Namir ShaabaniDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
Baisen ZengOmniAb Inc., Emeryville, CA 94608.
Michael BacicaLigand Pharmaceuticals, San Diego, CA 92121.
Wen ChenLigand Pharmaceuticals, San Diego, CA 92121.
Christopher WarnerLigand Pharmaceuticals, San Diego, CA 92121.
Jasmina RadoicicLigand Pharmaceuticals, San Diego, CA 92121.
Joongho JohSchool of Medicine, Department of Medicine, University of Louisville, Louisville, KY 40202.
Krishani Dinali PereraCollege of Veterinary Medicine, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506.
Huldah SangCollege of Veterinary Medicine, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506.
Tae KimCollege of Veterinary Medicine, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506.
Jianxiu YaoCollege of Veterinary Medicine, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506.
Fangzhu ZhaoDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0002-3172-1340
Devin SokDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-6711-9864
Jeff AllenLigand Pharmaceuticals, San Diego, CA 92121.ORCID 0009-0000-2664-008X
William HarrimanOmniAb Inc., Emeryville, CA 94608.
Waithaka MwangiCollege of Veterinary Medicine, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506.ORCID 0000-0002-2705-7571
Donghoon ChungSchool of Medicine, Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202.
John R TeijaroDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-8280-8887
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-7153-3769
H Jane DysonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0001-6855-3398
Peter E WrightDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0002-1368-0223
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0002-6469-2419
Kyeong-Ok ChangCollege of Veterinary Medicine, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506.ORCID 0000-0002-4435-3751
Duncan McGregorApplied Biomedical Science Institute, San Diego, CA 92127.
Vaughn V SmiderApplied Biomedical Science Institute, San Diego, CA 92127.ORCID 0000-0003-3488-6383
Scripps Research Institute · USKansas State University · USLigand Pharmaceuticals (United States) · USApplied Biotechnology Institute · USUniversity of Louisville · US
Funding
User Training & OutreachP30GM138396 · NIGMS · UCHICAGO ARGONNE, LLC · PI ROBERT F. FISCHETTI, JANET L. SMITH · 2020 to 2026
$34.3MX-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6MUser Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Gregory L Hura · 2017 to 2026
$28.6MSmall Molecule Protease Inhibitors against MERS-CoV and Coronaviruses of Pandemic PotentialR01AI130092 · NIAID · KANSAS STATE UNIVERSITY · PI Kyeong-Ok Chang, William Constantine Groutas · 2018 to 2026
$5.9MBroadly neutralizing SARS-CoV-2 peptidic knobsR01AI173109 · NIAID · APPLIED BIOMEDICAL SCIENCE INSTITUTE · PI Vaughn Vasil Smider · 2023 to 2026
$3.7MSmall Molecule Inhibitors Against 3C-Like Protease of SARS-CoV-2R01AI161085 · NIAID · KANSAS STATE UNIVERSITY · PI Kyeong-Ok Chang, William Constantine Groutas · 2021 to 2026
$3.7MMolecular and Structural Studies of Antibody Diversity MechanismsR01GM105826 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI SMIDER, VAUGHN VASIL · 2014 to 2021
$3.1MStructural Studies of Large Dynamic ComplexesR35GM131693 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DYSON, HELEN JANE · 2019 to 2023
$2.6MDefining clinically relevant viral epitopes with cow antibodiesR01HD088400 · NICHD · SCRIPPS RESEARCH INSTITUTE, THE · PI SMIDER, VAUGHN VASIL · 2017 to 2021
$1.8MPilatus 6mS10OD021832 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ADAMS, PAUL DAVID · 2016 to 2016
$980kA Fast Pixel-Array Pilatus 2M Detector for Automated Macromolecular Crystallography Data CollectionS10OD026941 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ADAMS, PAUL DAVID · 2019 to 2019
$563kUltralong CDR3 antibodies targeting exhausted T cellsR21AI144828 · NIAID · APPLIED BIOMEDICAL SCIENCE INSTITUTE · PI SMIDER, VAUGHN VASIL, TEIJARO, JOHN ROSS · 2020 to 2021
$538kNIAID NIH HHS R01 AI130092NIAID NIH HHS R01 AI161085NIAID NIH HHS R01 AI173109NIAID NIH HHS R21 AI144828NICHD NIH HHS R01 HD088400NIGMS NIH HHS P30 GM124169NIGMS NIH HHS P30 GM138396NIGMS NIH HHS P41 GM103393NIGMS NIH HHS R01 GM105826NIGMS NIH HHS R35 GM131693NIH HHS S10 OD021832NIH HHS S10 OD026941
Abstract
Cows produce antibodies with a disulfide-bonded antigen-binding domain embedded within ultralong heavy chain third complementarity determining regions. This "knob" domain is analogous to natural cysteine-rich peptides such as knottins in that it is small and stable but can accommodate diverse loops and disulfide bonding patterns. We immunized cattle with SARS-CoV-2 spike and found ultralong CDR H3 antibodies that could neutralize several viral variants at picomolar IC
Indexed as
COVID-19SARS-CoV-2AnimalsAntibodiesCattleDisulfidesFemaleImmunoglobulin Fab FragmentsAntibodiesDisulfidesImmunoglobulin Fab Fragmentscow antibodyimmunoglobulinknob peptidephage displayultralong CDR3
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