| Literature DB >> 26124093 |
Kristen E Pascal1, Christopher M Coleman2, Alejandro O Mujica1, Vishal Kamat1, Ashok Badithe1, Jeanette Fairhurst1, Charleen Hunt1, John Strein1, Alexander Berrebi3, Jeanne M Sisk2, Krystal L Matthews2, Robert Babb1, Gang Chen1, Ka-Man V Lai1, Tammy T Huang1, William Olson1, George D Yancopoulos4, Neil Stahl1, Matthew B Frieman2, Christos A Kyratsous4.
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.Entities:
Keywords: DPP4; MERS-CoV; Spike; mouse model; neutralizing antibody
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Year: 2015 PMID: 26124093 PMCID: PMC4507189 DOI: 10.1073/pnas.1510830112
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN: 0027-8424 Impact factor: 11.205