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Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8738-43. doi: 10.1073/pnas.1510830112. Epub 2015 Jun 29.

Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.

Author information

1
Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591;
2
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;
3
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201.
4
Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591; george@regeneron.com christos.kyratsous@regeneron.com.

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.

KEYWORDS:

DPP4; MERS-CoV; Spike; mouse model; neutralizing antibody

PMID:
26124093
PMCID:
PMC4507189
DOI:
10.1073/pnas.1510830112
[Indexed for MEDLINE]
Free PMC Article

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