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Development of human monoclonal antibody molecule for patients with highly pathogenic avian influenza(H5N1)

针对高致病性禽流感（H5N1）患者的人单克隆抗体分子的开发

基本信息

批准号：
18591120
负责人：
YAMASHIRO Tetsu
金额：
$ 2.28万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591120/
关键词：
phage display highly pathogenic avian influenza H5N1 Emerging and Re-emerging infectious diseases ファージティスプレイ法

项目摘要

Passive antibody therapy against H5N1 viruses could be a potentially adjunctive treatment option in human cases with H5N1 infection, because patients with Spanish flu pneumonia who had received transfusion with convalescent human serum products have been reported to reduce the risk of death. The objective of the study is to identify human monoclonal Fab with neutralizing potency against influenza A subtype H5N1 stains. Previously, we have constructed a human combinatorial Fab library using peripheral lymphocytes(PBLs) of a volunteer who had once infected with influenza A H5N1 and recovered. Identification of human Fab clones with neutralizing potency against HPAI H5N1 strains has been attempted using phage display technique with inactivated H5N1 virions isolated in Vietnam for biological enrichment(panning) and screening, however, was not successful. Recently, we have obtained a larger amount of PBLs from a healthy volunteer who had contracted H5N1 infection in May 2007 and recovered. Serum of the volunteer from which PBLs were isolated showed a high HI titer against an H5N1 year 2007 strain tested. A new human Fab library has been being constructed and efficient isolation of human monoclonal Fabs with neutralizing potency against H5N1 strains would be expected.

针对 H5N1 病毒的被动抗体治疗可能是 H5N1 感染人类病例的一种潜在辅助治疗选择，因为据报道，接受恢复期人血清产品输血的西班牙流感肺炎患者可降低死亡风险。该研究的目的是鉴定对甲型流感亚型 H5N1 染色剂具有中和效力的人单克隆 Fab。此前，我们利用一名曾感染甲型H5N1流感并康复的志愿者的外周淋巴细胞（PBL）构建了人类组合Fab文库。已尝试使用噬菌体展示技术对越南分离的灭活 H5N1 病毒粒子进行生物富集（淘选）和筛选，以鉴定对 HPAI H5N1 菌株具有中和效力的人类 Fab 克隆，但并未成功。最近，我们从一名2007年5月感染H5N1并康复的健康志愿者那里获得了大量的PBL。从中分离出 PBL 的志愿者血清显示出针对 2007 年测试的 H5N1 病毒株的高 HI 滴度。一个新的人类 Fab 文库正在构建中，有望有效分离出具有 H5N1 病毒株中和能力的人类单克隆 Fab。