Human 4F5 single-chain Fv antibody recognizing a conserved HA1 epitope has broad neutralizing potency against H5N1 influenza A viruses of different clades
Human 4F5 single-chain Fv antibody recognizing a conserved HA1 epitope has broad neutralizing potency against H5N1 influenza A viruses of different clades
复制标题
识别保守 HA1 表位的人 4F5 单链 Fv 抗体对不同分支的 H5N1 甲型流感病毒具有广泛的中和效力
DOI：
10.1016/j.antiviral.2013.05.001
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发表时间：
2013-08-01
影响因子：
7.6
通讯作者：
Jiao，Yongjun
中科院分区：
文献类型：
--
作者：
Zhang，Xiao;Qi，Xian;Jiao，Yongjun
甲型流感病毒对全世界的公共卫生构成重大威胁。针对保守表位的高亲和力人单链病毒抗体可能提供对多种病毒的免疫力，并保护人们免受未来大流行病毒的侵害。从H5N1病毒接种个体的淋巴细胞中产生了一个包含6.0 × 108个成员的噬菌体显示人单链病毒文库。利用重组H5N1病毒血凝素外结构域（HA1），鉴定出4F5 scFv对2支和9支H5N1病毒均具有中和活性。在鸡胚中，经预处理和后处理后，4F5 scFv的抗病毒活性分别使其对不同分支H5N1病毒的存活率达到100%和至少62.5%。根据IMGT数据库，4F5 scFv属于VH-3-43家族，在HA1中含有一半α-螺旋的肽（76）WLLGNP（81）被鉴定为结合口袋。这种新型广泛中和的单链病毒的保守结合表位可能成为设计和实施针对H5N1病毒的疫苗或RNA干扰的关键。
Influenza A viruses present a significant threat to public health worldwide. High-affinity human scFv antibodies against a conserved epitope can potentially provide immunity to diverse viruses and protect against future pandemic viruses. A library of phage-displayed human scFv containing 6.0 × 108members was generated from lymphocytes of H5N1 virus vaccinated individuals. Using the recombinant H5N1 virus hemagglutinin ectodomain (HA1), 4F5 scFv was identified with neutralizing activity against both clade 2 and 9 H5N1 viruses. In embryonated chicken eggs, the antiviral activity of 4F5 scFv conferred a 100% survival rate and at least a 62.5% survival rate against different clades of H5N1 viruses by pre-treatment and post-treatment, respectively. 4F5 scFv belongs to the VH-3-43 family according to the IMGT database, and a peptide (76)WLLGNP(81) containing half of an α-helix in HA1 was identified as the binding pocket. The conserved binding epitope of this novel broadly neutralizing scFv may become key in the design and implementation of vaccines or RNA interference against H5N1 viruses.