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

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, Matthew B. Frieman, Christos A. Kyratsous

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)8738-8743
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number28
DOIs
StatePublished - Jul 14 2015

Keywords

  • DPP4
  • MERS-CoV
  • Mouse model
  • Neutralizing antibody
  • Spike

ASJC Scopus subject areas

  • General

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  • Cite this

    Pascal, K. E., Coleman, C. M., Mujica, A. O., Kamat, V., Badithe, A., Fairhurst, J., Hunt, C., Strein, J., Berrebi, A., Sisk, J. M., Matthews, K. L., Babb, R., Chen, G., Lai, K. M. V., Huang, T. T., Olson, W., Yancopoulos, G. D., Stahl, N., Frieman, M. B., & 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 of the United States of America, 112(28), 8738-8743. https://doi.org/10.1073/pnas.1510830112