Escape From Monoclonal Antibody Neutralization Affects Henipavirus Fitness In Vitro and In Vivo
Escape From Monoclonal Antibody Neutralization Affects Henipavirus Fitness In Vitro and In Vivo
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DOI：
10.1093/infdis/jiv449
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发表时间：
2016-02-01
影响因子：
6.4
通讯作者：
Rockx, Barry
中科院分区：
文献类型：
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作者：
Borisevich, Viktoriya;Lee, Benhur;Rockx, Barry
亨尼帕病毒是人畜共患病毒，可引起人类严重和急性呼吸道疾病和脑炎。到目前为止，还没有疫苗或治疗方法被批准用于人类。中和抗体的存在与动物对致死性疾病的保护密切相关。然而，由于RNA病毒易于发生高突变率，因此这些病毒逃避中和的可能性仍然是一个潜在的问题。在本研究中，我们使用6种不同的单克隆抗体产生中和逃逸突变体，并研究了这些中和逃逸突变体对体外和体内适应性的影响。这些数据提供了通过使用交叉中和单克隆抗体的混合物来克服中和逃逸的机制，所述交叉中和单克隆抗体识别糖蛋白内对病毒复制和毒力重要的残基。
Henipaviruses are zoonotic viruses that can cause severe and acute respiratory diseases and encephalitis in humans. To date, no vaccine or treatments are approved for human use. The presence of neutralizing antibodies is a strong correlate of protection against lethal disease in animals. However, since RNA viruses are prone to high mutation rates, the possibility that these viruses will escape neutralization remains a potential concern. In the present study, we generated neutralization-escape mutants, using 6 different monoclonal antibodies, and studied the effect of these neutralization-escape mutations on in vitro and in vivo fitness. These data provide a mechanism for overcoming neutralization escape by use of cocktails of cross-neutralizing monoclonal antibodies that recognize residues within the glycoprotein that are important for virus replication and virulence.