#Structural and #molecular #basis for #Ebola #virus #neutralization by protective #human #antibodies (Science, abstract)

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

John Misasi 1,5,8*, Morgan S. A. Gilman 2,*, Masaru Kanekiyo 1,*, Miao Gui 4*Alberto Cagigi 1Sabue Mulangu 1Davide Corti 6Julie E. Ledgerwood 1Antonio Lanzavecchia 6,9James Cunningham 5Jean Jacques Muyembe-Tamfun 7Ulrich Baxa 3,Barney S. Graham 1Ye Xiang 4Nancy J. Sullivan 1Jason S. McLellan 2

Author Affiliations: 1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 2Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.3Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. 4Centre for Infectious Diseases Research, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084 China. 5Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. 6Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. 7National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo. 8Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA 02215, USA. 9Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland.

Corresponding author. E-mail: njsull@mail.nih.gov (N.J.S.); yxiang@mail.tsinghua.edu.cn (Y.X.)

* These authors contributed equally to this work.

These authors contributed equally to this work.

Science  18 Mar 2016: Vol. 351, Issue 6279, pp. 1343-1346 / DOI: 10.1126/science.aad6117

 

Antibodies block Ebola virus entry

The recent Ebola virus outbreak in West Africa illustrates the need for both an effective vaccine and therapies to treat infected individuals. Corti et al. isolated two monoclonal antibodies from a survivor of the 1995 Kikwit outbreak and demonstrated their therapeutic efficacy in Ebola virus–infected macaques. In fact, one antibody protected macaques when it was given up to 5 days after infection. Misasi et al. solved the crystal structures of fragments of the two antibodies bound to the Ebola virus glycoprotein (GP), which mediates viral cell entry. The two antibodies targeted different regions of GP, but in both cases blocked steps required for viral entry.

Science, this issue pp. 1339 & 1343

 

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.

Keywords: Research; Abstracts; Ebola; Monoclonal Antibodes.

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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.