A “Trojan horse” bispecific-antibody strategy for broad protection against ebolaviruses
Abstract
The recent major Ebola virus outbreak in West Africa high-lighted the need for effective therapeutics against this and other filoviruses. Neutralizing ebolaviruses with antibodies is a challenge because the viruses bind their entry receptor, NPC1, inside the cell within endosomes rather than on the cell surface. Furthermore, enzymes in endosomes cleave the Ebola virus surface glycoprotein (GP) to reveal its receptor binding site. Wec et al. now report a bispecific antibody strategy targeting all known ebolaviruses that overcomes this problem (see the Perspective by Labrijn and Parren). They coupled an antibody specific for a conserved, surface-exposed epitope of GP to antibodies that recognize either NPC1 or the NPC1 binding site on GP. Treating mice therapeutically with these antibodies allowed them to survive otherwise lethal ebolavirus infection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 21, 2016
- Source ID
- 10.1126/science.aag3267
Entities
People
- Ana I. Kuehne
- Andrew I. Flyak
- Andrew S Herbert
- Anna Z Wec
- Elisabeth K. Nyakatura
- Erica Ollmann Saphire
- Eva Mittler
- Frederick W Holtsberg
- James E. Crowe, Jr.
- John M Dye
- John R. Christin
- Jonathan R Lai
- Kartik Chandran
- Katie A. Howell
- M. Javad Aman
- Rohit K Jangra
- Russell R. Bakken
- Sergey Shulenin
- Sushma Bharrhan
- Zachary A. Bornholdt
Organizations
- Albert Einstein College of Medicine
- Defense Threat Reduction Agency
- German Academic Exchange Service
- National Institutes of Health
- Scripps Research
- United States Army Medical Research Institute of Infectious Diseases
- Vanderbilt University