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Science. 2016 Oct 21;354(6310):350-354. Epub 2016 Sep 8.

A "Trojan horse" bispecific-antibody strategy for broad protection against ebolaviruses.

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
2
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
3
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
4
Integrated Biotherapeutics Inc., Gaithersburg, MD 20878, USA.
5
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
6
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 10550, USA.
7
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37235, USA.
8
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 10550, USA.
9
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37235, USA. kartik.chandran@einstein.yu.edu jon.lai@einstein.yu.edu john.m.dye1.civ@mail.mil javad@integratedbiotherapeutics.com james.crowe@vanderbilt.edu.
10
Department of Pediatrics, Vanderbilt University, Nashville, TN 37232, USA.
11
Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
12
Integrated Biotherapeutics Inc., Gaithersburg, MD 20878, USA. kartik.chandran@einstein.yu.edu jon.lai@einstein.yu.edu john.m.dye1.civ@mail.mil javad@integratedbiotherapeutics.com james.crowe@vanderbilt.edu.
13
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. kartik.chandran@einstein.yu.edu jon.lai@einstein.yu.edu john.m.dye1.civ@mail.mil javad@integratedbiotherapeutics.com james.crowe@vanderbilt.edu.
14
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kartik.chandran@einstein.yu.edu jon.lai@einstein.yu.edu john.m.dye1.civ@mail.mil javad@integratedbiotherapeutics.com james.crowe@vanderbilt.edu.
15
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kartik.chandran@einstein.yu.edu jon.lai@einstein.yu.edu john.m.dye1.civ@mail.mil javad@integratedbiotherapeutics.com james.crowe@vanderbilt.edu.

Abstract

There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific-antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope. Bispecific antibodies, but not parent mAbs, neutralized all known ebolaviruses by coopting viral particles themselves for endosomal delivery and conferred postexposure protection against multiple ebolaviruses in mice. Such "Trojan horse" bispecific antibodies have potential as broad antifilovirus immunotherapeutics.

Comment in

PMID:
27608667
PMCID:
PMC5647781
DOI:
10.1126/science.aag3267
[Indexed for MEDLINE]
Free PMC Article

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