Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection
- 29 June 2015
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 112 (28), 8738-8743
- https://doi.org/10.1073/pnas.1510830112
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.Keywords
Funding Information
- Regeneron Pharmaceuticals, Inc. (N/A)
This publication has 44 references indexed in Scilit:
- Emergence of the Middle East Respiratory Syndrome CoronavirusPLoS Pathogens, 2013
- Coronaviruses Lacking Exoribonuclease Activity Are Susceptible to Lethal Mutagenesis: Evidence for Proofreading and Potential TherapeuticsPLoS Pathogens, 2013
- Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4Cell Research, 2013
- The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing AntibodiesJournal of Virology, 2013
- Induction of Alternatively Activated Macrophages Enhances Pathogenesis during Severe Acute Respiratory Syndrome Coronavirus InfectionJournal of Virology, 2012
- Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome CoronavirusThe Journal of Infectious Diseases, 2010
- The growth and potential of human antiviral monoclonal antibody therapeuticsNature Biotechnology, 2007
- High Fidelity of Murine Hepatitis Virus Replication Is Decreased in nsp14 Exoribonuclease MutantsJournal of Virology, 2007
- High-throughput engineering of the mouse genome coupled with high-resolution expression analysisNature Biotechnology, 2003
- A guardian angel: the involvement of dipeptidyl peptidase IV in psychoneuroendocrine function, nutrition and immune defenceClinical Science, 2000