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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 ? 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.

SUBMITTER: Pascal KE 

PROVIDER: S-EPMC4507189 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Pascal Kristen E KE   Coleman Christopher M CM   Mujica Alejandro O AO   Kamat Vishal V   Badithe Ashok A   Fairhurst Jeanette J   Hunt Charleen C   Strein John J   Berrebi Alexander A   Sisk Jeanne M JM   Matthews Krystal L KL   Babb Robert R   Chen Gang G   Lai Ka-Man V KM   Huang Tammy T TT   Olson William W   Yancopoulos George D GD   Stahl Neil N   Frieman Matthew B MB   Kyratsous Christos A CA  

Proceedings of the National Academy of Sciences of the United States of America 20150629 28


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  ...[more]

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