title: Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.
abstract: Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pascal
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Coleman
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Alejandro O
authors.initials: AO
authors.lastname: Mujica
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Vishal
authors.initials: V
authors.lastname: Kamat
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Ashok
authors.initials: A
authors.lastname: Badithe
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Jeanette
authors.initials: J
authors.lastname: Fairhurst
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Charleen
authors.initials: C
authors.lastname: Hunt
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: John
authors.initials: J
authors.lastname: Strein
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Alexander
authors.initials: A
authors.lastname: Berrebi
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Sisk
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Krystal L
authors.initials: KL
authors.lastname: Matthews
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Robert
authors.initials: R
authors.lastname: Babb
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Ka-Man V
authors.initials: KM
authors.lastname: Lai
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Tammy T
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: William
authors.initials: W
authors.lastname: Olson
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591; george@regeneron.com christos.kyratsous@regeneron.com.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
authors.forename: Neil
authors.initials: N
authors.lastname: Stahl
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Frieman
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591; george@regeneron.com christos.kyratsous@regeneron.com.
authors.forename: Christos A
authors.initials: CA
authors.lastname: Kyratsous
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use*; D018352:Coronavirus Infections / Q000628:therapy* / Q000821:virology; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology / Q000472:pathogenicity*; D064370:Spike Glycoprotein, Coronavirus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D064370:Spike Glycoprotein, Coronavirus
keywords: DPP4; MERS-CoV; Spike; mouse model; neutralizing antibody