James Crowe
Faculty Member
Last active: 3/31/2020

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

Wec AZ, Nyakatura EK, Herbert AS, Howell KA, Holtsberg FW, Bakken RR, Mittler E, Christin JR, Shulenin S, Jangra RK, Bharrhan S, Kuehne AI, Bornholdt ZA, Flyak AI, Saphire EO, Crowe JE, Aman MJ, Dye JM, Lai JR, Chandran K
Science. 2016 354 (6310): 350-354

PMID: 27608667 · PMCID: PMC5647781 · DOI:10.1126/science.aag3267

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.

Copyright © 2016, American Association for the Advancement of Science.

MeSH Terms (20)

Animals Antibodies, Bispecific Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Binding Sites Carrier Proteins Cell Line, Tumor Ebolavirus Endosomes Hemorrhagic Fever, Ebola Humans Immunotherapy Intracellular Signaling Peptides and Proteins Membrane Glycoproteins Mice Mice, Inbred BALB C Receptors, Virus Viral Envelope Proteins Virus Internalization

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