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PMID: 20304456 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms.

Virology ·Vol. 401 ·No. 2 ·2010-06-05 ·Pages 228-35

Shedlock DJ, Bailey MA, Popernack PM, Cunningham JM, Burton DR, Sullivan NJ

Abstract

Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.

MeSH Terms
Animals Antibodies, Monoclonal/immunology Antibodies, Neutralizing/immunology Antibodies, Viral/immunology Ebolavirus/immunology Epitopes/immunology Haplorhini Humans Neutralization Tests Protein Binding Viral Envelope Proteins/immunology
Chemicals
Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Epitopes Viral Envelope Proteins envelope glycoprotein, Ebola virus
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Shedlock Devon J
Biodefense Research Section, Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, 40 Convent Drive, MSC 3005, Bethesda, MD 20814, USA. shedlock@mail.med.upenn.edu
Bailey Michael A
Popernack Paul M
Cunningham James M
Burton Dennis R
Sullivan Nancy J
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Article Info
Journal
Virology
Abbr.
Virology
ISSN
1096-0341
DOI
10.1016/j.virol.2010.02.029
Email
shedlock@mail.med.upenn.edu
Published
2010-06-05
Epub
2010-00-20
Pages
228-35
Language
English
Region
United States
NLM ID
0110674
PMCID
PMC3351102
Subset
IM
Grants
Intramural NIH HHS · ZIA AI005081-05 · United States
Intramural NIH HHS · ZIA AI005082-05 · United States
NIAID NIH HHS · AI048053 · United States
NIAID NIH HHS · R01 AI048053 · United States
Intramural NIH HHS · ZIA AI005079-05 · United States
External Links
PubMed source DOI: 10.1016/j.virol.2010.02.029 PMC Full Text
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