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

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

Abstract

© 2015, National Academy of Sciences. All rights reserved. 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.

Citation

Pascal, K. E., Coleman, C. M., Mujica, A. O., Kamat, V., Badithe, A., Fairhurst, J., …Kyratsous, C. A. (2015). Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection. Proceedings of the National Academy of Sciences, 112(28), 8738-8743. https://doi.org/10.1073/pnas.1510830112

• Journal Article Type: Article
• Acceptance Date: Jun 2, 2015
• Online Publication Date: Jun 29, 2015
• Publication Date: Jul 14, 2015
• Deposit Date: Dec 17, 2019
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Print ISSN: 0027-8424
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 112
• Issue: 28
• Pages: 8738-8743
• DOI: https://doi.org/10.1073/pnas.1510830112
• Public URL: https://nottingham-repository.worktribe.com/output/3590119