dc.contributor
Institut Català de la Salut
dc.contributor
[Hastie KM] Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA. [Salie Z] Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA. Eli Lilly, San Diego, CA, USA. [Ke Z] Division of Structural Studies, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. Department of Cell and Virus Structure, Max Planck Institute of Biochemistry, Martinsried, Munich, Germany. Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX, USA. [Halfmann PJ] Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. [DeWald LE] Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA. [McArdle S] Microscopy Core, La Jolla Institute for Immunology, La Jolla, La Jolla, CA, USA. [Grinyó A] Integral Molecular, Philadelphia, PA, USA. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Hospital del Mar Research Institute, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Hastie, Kathryn
dc.contributor.author
Li, Zhe
dc.contributor.author
Ke, Zunlong
dc.contributor.author
Halfmann, Peter
dc.contributor.author
DeWald, Lisa Evans
dc.contributor.author
McArdle, Sara
dc.contributor.author
Grinyo i Escuer, Ariadna
dc.date.accessioned
2025-10-25T05:37:11Z
dc.date.available
2025-10-25T05:37:11Z
dc.date.issued
2025-04-08T07:04:12Z
dc.date.issued
2025-04-08T07:04:12Z
dc.date.issued
2025-02-03
dc.identifier
Hastie KM, Salie ZL, Ke Z, Halfmann PJ, DeWald LE, McArdle S, et al. Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane. Nat Commun. 2025 Feb 3;16:1293.
dc.identifier
http://hdl.handle.net/11351/12905
dc.identifier
10.1038/s41467-025-56452-2
dc.identifier
001413840600042
dc.identifier.uri
http://hdl.handle.net/11351/12905
dc.description.abstract
Ebola virus; Virion membrane
dc.description.abstract
Virus del Ébola; Membrana del virión
dc.description.abstract
Virus de l'Ebola; Membrana del virió
dc.description.abstract
Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP1,2) are the standard of care for Ebola virus disease (EVD). Anti-GP1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP1,2 epitope that has evaded structural characterization. Using X-ray crystallography and cryo-electron tomography of mAb 3A6 complexed with its stalk-MPER epitope, we reveal a previously undescribed mechanism in which 3A6 binds to a conformation of GP1,2 that is lifted from the virion membrane. We further show that in both domestic guinea pig and rhesus monkey EVD models, 3A6 provides therapeutic benefit at high-viremia advanced disease stages and at the lowest dose yet demonstrated for any anti-EBOV mAb-based monotherapy. The findings reported here can guide design of next-generation highly potent anti-EBOV therapeutics and vaccines.
dc.description.abstract
Open access funding provided by the National Institutes of Health.
dc.format
application/pdf
dc.publisher
Nature Portfolio
dc.relation
Nature Communications;16
dc.relation
https://doi.org/10.1038/s41467-025-56452-2
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Anticossos monoclonals - Ús terapèutic
dc.subject
Malaltia de l'Ebola - Prevenció
dc.subject
Rates (Animals de laboratori)
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Neutralizing
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Other subheadings::Other subheadings::/therapeutic use
dc.subject
DISEASES::Virus Diseases::RNA Virus Infections::Hemorrhagic Fevers, Viral::Hemorrhagic Fever, Ebola
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Other subheadings::Other subheadings::Other subheadings::/prevention & control
dc.subject
ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos neutralizantes
dc.subject
Otros calificadores::Otros calificadores::/uso terapéutico
dc.subject
ENFERMEDADES::virosis::infecciones por virus ARN::fiebres hemorrágicas víricas::fiebre hemorrágica de Ébola
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/prevención & control
dc.subject
ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones
dc.title
Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
