ArticleImmunity2020
Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization.
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Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61citing papers in PubMed
1.8field-weighted citation impact, top 8% of its field
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Who cites it
61 citing papers in PubMed, 94 citations in OpenAlex.
- Host-virus determinants of Ebola virus persistence in a human cerebral organoid model.Nature microbiology · 2026Article
- A broadly-neutralizing antibody against Orthoebolavirus glycoprotein that potentiates the breadth and neutralization of other antibodies.Npj viruses · 2026Article
- Nanobody targeting glycan cap confers broad orthoebolavirus neutralization.Virologica Sinica · 2026Article
- Epitope-focused discovery of SARS-CoV-2 antibodies that potently neutralize Omicron variants.Nature microbiology · 2026Article
- Article
- Rational design of next-generation filovirus vaccines combining glycoprotein stabilization and nanoparticle display with glycan modification.Nature communications · 2025Article
- Immunogenicity of Adalimumab in Bacterial Molecular Mimicry: In Silico Analysis.JMIR bioinformatics and biotechnology · 2025Article
- Rational design of next-generation filovirus vaccines through glycoprotein stabilization, nanoparticle display, and glycan modification.bioRxiv : the preprint server for biology · 2025Article
- A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade.Cell reports. Medicine · 2025Article
- Treatment of Ebola Virus Disease: From Serotherapy to the Use of Monoclonal Antibodies.Antibodies (Basel, Switzerland) · 2025Review
- Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection.PLoS pathogens · 2024Article
- Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV.The Journal of clinical investigation · 2024Article
- Monoclonal antibodies: From magic bullet to precision weapon.Molecular biomedicine · 2024Review
- An update on nonhuman primate usage for drug and vaccine evaluation against filoviruses.Expert opinion on drug discovery · 2024Review
- Afucosylated anti-EBOV antibody MIL77-3 engages sGP to elicit NK cytotoxicity.Journal of virology · 2024Article
- Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies.Nature microbiology · 2024Article
- Macaque antibodies targeting Marburg virus glycoprotein induced by multivalent immunization.Journal of virology · 2024Article
- Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement systemCommunications biology · 2024Article
- Targeting host O-linked glycan biosynthesis affects Ebola virus replication efficiency and reveals differential GalNAc-T acceptor site preferences on the Ebola virus glycoprotein.Journal of virology · 2024Article
- Monoclonal Antibodies as a Therapeutic Strategy against Multidrug-Resistant Bacterial Infections in a Post-COVID-19 Era.Life (Basel, Switzerland) · 2024Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 9 institutions in 2 countries.
Pavlo GilchukVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Charles D MurinDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jacob C MilliganDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Robert W CrossGalveston National Laboratory, Galveston, TX 77550, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Chad E MireGalveston National Laboratory, Galveston, TX 77550, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Philipp A IlinykhGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Kai HuangGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Natalia KuzminaGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Pilar X AltmanDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sean HuiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bronwyn M GunnRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Aubrey L BryanIntegral Molecular, Inc., Philadelphia, PA 19104, USA.
Edgar DavidsonIntegral Molecular, Inc., Philadelphia, PA 19104, USA.
Benjamin J DoranzIntegral Molecular, Inc., Philadelphia, PA 19104, USA.
Hannah L TurnerDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tanwee AlkutkarDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Robin FlinkoDivision of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Chiara OrlandiDivision of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Robert CarnahanVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Rachel NargiVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Robin G BombardiVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Megan E VodzakVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Sheng LiDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Adaora OkoliFirst Consultants Medical Center, Lagos, Nigeria.
Morris IbeawuchiFirst Consultants Medical Center, Lagos, Nigeria.
Benjamin OhiaeriFirst Consultants Medical Center, Lagos, Nigeria.
George K LewisDivision of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Galit AlterRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Alexander BukreyevGalveston National Laboratory, Galveston, TX 77550, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Erica Ollmann SaphireDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Thomas W GeisbertGalveston National Laboratory, Galveston, TX 77550, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
James E CroweVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vumc.org.
Scripps Research Institute · USGalveston College · USVanderbilt University Medical Center · USFirst Consultants Medical Center · NGIntegral Molecular (United States) · USUniversity of Maryland, Baltimore · USRagon Institute of MGH, MIT and Harvard · USThe University of Texas Medical Branch at Galveston · USUniversity of California, San Diego · US
Funding
Regulatory Compliance Core - Galveston National Laboratory BSL4 OperationsUC7AI094660 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Gene Garrard Olinger · 2011 to 2026
$208.8MTumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8MVANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MSpecific and Broadly Active Monoclonal Antibody Therapeutics Against The FilovirusesU19AI142790 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI ALTER, GALIT · 2019 to 2023
$40.0MResearch Project 3: siRNA Therapy and Small Molecule Combination Treatment for FilovirusesU19AI142785 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GEISBERT, THOMAS WILLIAM · 2019 to 2023
$35.5MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MMechanistic Virology CoreU19AI109762 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI SAPHIRE, ERICA OLLMANN · 2014 to 2018
$29.6MSupplemental Research Project (SRP)U19AI109711 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GEISBERT, THOMAS WILLIAM · 2014 to 2018
$26.6MUniversity of California Launching Future Leaders in Global Health Research Training ProgramD43TW009343 · FIC · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIG R COHEN, Sung-Jae Lee · 2017 to 2026
$14.7MProject 3- Mucosal Determinants of Virus TransmissionP01AI124912 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI GALLO, ROBERT C · 2016 to 2019
$14.4MEBOLA VIRAL GLYCOPROTEINS: STRUCTURAL ANALYSISR01AI067927 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI SAPHIRE, ERICA OLLMANN · 2006 to 2013
$3.6MFIC NIH HHS D43 TW009343NCATS NIH HHS UL1 TR000445NCI NIH HHS P30 CA068485NCRR NIH HHS UL1 RR024975NIAID NIH HHS HHSN272201400058CNIAID NIH HHS P01 AI124912NIAID NIH HHS R01 AI067927NIAID NIH HHS U19 AI109711NIAID NIH HHS U19 AI109762NIAID NIH HHS U19 AI142785NIAID NIH HHS U19 AI142790NIAID NIH HHS UC7 AI094660NIDDK NIH HHS P30 DK058404NIH HHS S10 OD021737
Abstract
Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus. We systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mAbs that cooperatively bound to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a conserved epitope on the GP base region. mAb rEBOV-548 bound to a glycan cap epitope, possessed neutralizing and Fc-mediated effector function activities, and potentiated neutralization by rEBOV-520. Remodeling of the glycan cap structures by the cocktail enabled enhanced GP binding and virus neutralization. The cocktail demonstrated resistance to virus escape and protected non-human primates (NHPs) against Ebola virus disease. These data illuminate structural principles of antibody cooperativity with implications for development of antiviral immunotherapeutics.
Indexed as
AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCell LineDisease Models, AnimalDrug Therapy, CombinationEbolavirusEpitopesFemaleGlycoproteinsHemorrhagic Fever, EbolaHumansImmunoglobulin Fab FragmentsMacaca mulattaMaleAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesGlycoproteinsImmunoglobulin Fab Fragmentsantibody synergyantibody therapeuticscooperative neutralizationEbolavirusebolavirus infectionepitope mappingglycoproteinmolecular mimicryneutralizing antibodiesviral antibodies
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