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

针对刺突蛋白的全人源抗体在新型人源化 MERS-CoV 感染小鼠模型中的暴露前和暴露后疗效

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作者:Kristen E Pascal, Christopher M Coleman, Alejandro O Mujica, Vishal Kamat, Ashok Badithe, Jeanette Fairhurst, Charleen Hunt, John Strein, Alexander Berrebi, Jeanne M Sisk, Krystal L Matthews, Robert Babb, Gang Chen, Ka-Man V Lai, Tammy T Huang, William Olson, George D Yancopoulos, Neil Stahl, Matthe

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.

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