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

被引：179

作者：

Pascal, Kristen E. ^{[1
]}

Coleman, Christopher M. ^{[2
]}

Mujica, Alejandro O. ^{[1
]}

Kamat, Vishal ^{[1
]}

Badithe, Ashok ^{[1
]}

Fairhurst, Jeanette ^{[1
]}

Hunt, Charleen ^{[1
]}

Strein, John ^{[1
]}

Berrebi, Alexander ^{[3
]}

Sisk, Jeanne M. ^{[2
]}

Matthews, Krystal L. ^{[2
]}

Babb, Robert ^{[1
]}

Chen, Gang ^{[1
]}

Lai, Ka-Man V. ^{[1
]}

Huang, Tammy T. ^{[1
]}

Olson, William ^{[1
]}

Yancopoulos, George D. ^{[1
]}

Stahl, Neil ^{[1
]}

Frieman, Matthew B. ^{[2
]}

Kyratsous, Christos A. ^{[1
]}

机构：

[1] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

[2] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA

[3] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2015年 / 112卷 / 28期

关键词：

MERS-CoV; Spike; DPP4; neutralizing antibody; mouse model; RESPIRATORY SYNDROME CORONAVIRUS; DIPEPTIDYL PEPTIDASE 4; NEUTRALIZING ANTIBODIES; IMMUNOGLOBULIN GENES; FUNCTIONAL RECEPTOR; SAUDI-ARABIA; MICE; REPLICATION; GENERATION; VIRUS;

D O I：

10.1073/pnas.1510830112

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：8738 / 8743

页数：6

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