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抗 A(H7N9) 流感病毒 HA 单克隆抗体的鉴定。

Characterization of Mouse Monoclonal Antibodies Against the HA of A(H7N9) Influenza Virus.

机构信息

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.

TAUNS Laboratories, Inc., Izunokuni, Shizuoka 410-2325, Japan.

出版信息

Viruses. 2019 Feb 11;11(2):149. doi: 10.3390/v11020149.

Abstract

Many cases of human infection with the H7N9 virus have been detected in China since 2013. H7N9 viruses are maintained in chickens and are transmitted to humans at live bird markets. During circulation in birds, H7N9 viruses have accumulated amino acid substitutions in their hemagglutinin (HA), which resulted in an antigenically change in the recent H7N9 viruses. Here, we characterized 46 mouse monoclonal antibodies against the HA of the prototype strain. 16 H7-HA-specific monoclonal antibodies (mAbs) possessed hemagglutination inhibition (HI) and neutralization activities by recognizing the major antigenic site A; four other H7-HA-specific clones also showed HI and neutralizing activities via recognition of the major antigenic sites A and D; seven mAbs that reacted with several HA subtypes and possibly recognized the HA stem partially protected mice from lethal infection with prototype H7N9 virus; and the remaining 19 mAbs had neither HI nor neutralization activity. All human H7N9 viruses tested showed a similar neutralization sensitivity to the first group of 16 mAbs, whereas human H7N9 viruses isolated in 2016‒2017 were not neutralized by a second group of 4 mAbs. These results suggest that amino acid substitutions at the epitope of the second mAb group appear to be involved in the antigenic drift of the H7N9 viruses. Further analysis is required to fully understand the antigenic change in H7N9 viruses.

摘要

自 2013 年以来,中国已检测到多起人类感染 H7N9 病毒的病例。H7N9 病毒在鸡群中存在,并在活禽市场传播给人类。在禽类中传播时,H7N9 病毒在其血凝素(HA)中积累了氨基酸替换,导致最近的 H7N9 病毒发生抗原变化。在此,我们对原型株的 HA 进行了 46 株鼠源性单克隆抗体的鉴定。16 株 H7-HA 特异性单克隆抗体(mAb)通过识别主要抗原表位 A 具有血凝抑制(HI)和中和活性;另外 4 株 H7-HA 特异性克隆也通过识别主要抗原表位 A 和 D 具有 HI 和中和活性;7 株与多种 HA 亚型反应的 mAb 可能部分识别 HA 茎,可保护小鼠免受原型 H7N9 病毒的致死性感染;其余 19 株 mAb 既无 HI 也无中和活性。所有测试的人源 H7N9 病毒对第一组 16 株 mAb 表现出相似的中和敏感性,而 2016-2017 年分离的人源 H7N9 病毒则不能被第二组 4 株 mAb 中和。这些结果表明,第二组 mAb 表位的氨基酸替换可能参与了 H7N9 病毒的抗原漂移。需要进一步分析以全面了解 H7N9 病毒的抗原变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ef8/6410113/666cbd9ead6e/viruses-11-00149-g001.jpg

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