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

作者：Kristen E. Pascal, Christopher M. Coleman, Alejandro O. Mujica, Vishal Kamat, Ashok Badithe, Jeanette Fairhurst, Charleen Hunt, John Strein, Alexander A. Berrebi, Jeanne M. Sisk, Krystal Matthews, Robert Babb, Gang Chen, Ka-Man V. Lai, Tammy Huang, William C. Olson, George D. Yancopoulos, Neil Stahl, Matthew B. Frieman, Christos A. Kyratsous · 发表于：Proceedings of the National Academy of Sciences · 年份：2015 · DOI：10.1073/pnas.1510830112 · 被引用次数：224 · 研究领域：SARS-CoV-2 and COVID-19 Research、Viral gastroenteritis research and epidemiology、Animal Virus Infections Studies

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.