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TitleAntibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses.
Journal, issue, pagesCell, Vol. 169, Issue 5, Page 878-890.e15, Year 2017
Publish dateMay 18, 2017
AuthorsAnna Z Wec / Andrew S Herbert / Charles D Murin / Elisabeth K Nyakatura / Dafna M Abelson / J Maximilian Fels / Shihua He / Rebekah M James / Marc-Antoine de La Vega / Wenjun Zhu / Russell R Bakken / Eileen Goodwin / Hannah L Turner / Rohit K Jangra / Larry Zeitlin / Xiangguo Qiu / Jonathan R Lai / Laura M Walker / Andrew B Ward / John M Dye / Kartik Chandran / Zachary A Bornholdt /
PubMed AbstractExperimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has ...Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GP) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GP recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.
External linksCell / PubMed:28525755 / PubMed Central
MethodsEM (single particle)
Resolution18.2 - 25.3 Å
Structure data

EMDB-8698:
EBOV GPdMuc:ADI-16061
Method: EM (single particle) / Resolution: 25.3 Å

EMDB-8699:
EBOV GPdMuc in complex with ADI-15742 Fab
Method: EM (single particle) / Resolution: 20.8 Å

EMDB-8700:
EBOV GPdMuc:ADI-15878
Method: EM (single particle) / Resolution: 18.2 Å

EMDB-8701:
EBOV GPdMuc:ADI-15946
Method: EM (single particle) / Resolution: 24.7 Å

Source
  • Homo sapiens (human)

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