Structural and molecular basis for Ebola virus neutralization by protective human antibodies.

Abstract

Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

• Authors: John Misasi, Morgan S A Gilman, Masaru Kanekiyo, Miao Gui, Alberto Cagigi, Sabue Mulangu, Davide Corti, Julie E Ledgerwood, Antonio Lanzavecchia, James Cunningham, Jean Jacques Muyembe-Tamfun, Ulrich Baxa, Barney S Graham, Ye Xiang, Nancy J Sullivan, Jason S McLellan
• Journal: Science (New York, N.Y.) (Science) Vol. 351 Issue 6279 Pg. 1343-6 (Mar 18 2016) ISSN: 1095-9203 [Electronic] United States
• PMID: 26917592 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2016, American Association for the Advancement of Science.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral
• Viral Envelope Proteins
• envelope glycoprotein, Ebola virus
• Cathepsins

Topics

• Antibodies, Monoclonal (chemistry, immunology)
• Antibodies, Neutralizing (chemistry, immunology)
• Antibodies, Viral (chemistry, immunology)
• Cathepsins (chemistry)
• Cryoelectron Microscopy
• Crystallography, X-Ray
• Ebolavirus (immunology)
• Hemorrhagic Fever, Ebola (immunology, prevention & control)
• Humans
• Protein Conformation
• Proteolysis
• Viral Envelope Proteins (chemistry, immunology)