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Pan-ebolavirus protective therapy by two multifunctional human antibodies
- Source :
- Cell
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Ebolaviruses cause a severe and often fatal illness with the potential for global spread. Monoclonal antibody-based treatments that have become available recently have a narrow therapeutic spectrum and are ineffective against ebolaviruses other than Ebola virus (EBOV), including medically important Bundibugyo (BDBV) and Sudan (SUDV) viruses. Here, we report the development of a therapeutic cocktail comprising two broadly neutralizing human antibodies, rEBOV-515 and rEBOV-442, that recognize non-overlapping sites on the ebolavirus glycoprotein (GP). Antibodies in the cocktail exhibited synergistic neutralizing activity, resisted viral escape, and possessed differing requirements for their Fc-regions for optimal in vivo activities. The cocktail protected non-human primates from ebolavirus disease caused by EBOV, BDBV, or SUDV with high therapeutic effectiveness. High-resolution structures of the cocktail antibodies in complex with GP revealed the molecular determinants for neutralization breadth and potency. This study provides advanced preclinical data to support clinical development of this cocktail for pan-ebolavirus therapy.
- Subjects :
- Models, Molecular
Primates
medicine.drug_class
Receptors, Fc
Antibodies, Viral
medicine.disease_cause
Monoclonal antibody
Article
General Biochemistry, Genetics and Molecular Biology
Neutralization
Cell Line
Epitopes
medicine
Animals
Humans
Amino Acid Sequence
Viremia
Glycoproteins
Ebolavirus
chemistry.chemical_classification
Mice, Inbred BALB C
Binding Sites
Ebola virus
biology
Cryoelectron Microscopy
Antibodies, Monoclonal
Hemorrhagic Fever, Ebola
Hydrogen-Ion Concentration
Antibodies, Neutralizing
Preclinical data
Virology
Recombinant Proteins
Epitope mapping
chemistry
biology.protein
Female
Antibody
Glycoprotein
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 184
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....27aff7c8ca9e2194162d2c18ad4dc610