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.
Funding Information
  • Intramural Research Program of the Vaccine Research Center
  • National Institute of Allergy and Infectious Diseases
  • NIH (NIH-5K08AI079381)
  • Boston Children's Hospital Faculty Development
  • National Institute of General Medical Sciences of the National Institutes of Health (T32GM008704)
  • 973 Program (2015CB14010102)
  • National Natural Science Foundation of China (81550001, 31470721)
  • Junior Thousand Talents Program of China (20131770418)
  • Frederick National Laboratory for Cancer Research
  • National Institutes of Health (HHSN261200800001E)