Neutralizing human monoclonal antibodies to hepatitis A virus recovered by phage display
Neutralizing human monoclonal antibodies to hepatitis A virus recovered by phage display
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DOI：
10.1016/j.virol.2003.10.014
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发表时间：
2004-01-20
期刊：
影响因子：
3.7
通讯作者：
Hong, HJ
中科院分区：
文献类型：
--
作者：
Kim, SJ;Jang, MH;Hong, HJ
从甲型肝炎病毒（HAV）免疫供者外周血淋巴细胞（PBLs）构建的噬菌体抗体文库中分离到四种人抗甲型肝炎病毒（HAV）单克隆抗体（mab）。4种单克隆抗体的亲和力存在差异，经过4轮筛选，其中2种单克隆抗体（HA6、HA9）具有优势，且亲和性高于其他2种单克隆抗体（HA1、HA12）。四种单克隆抗体在放射免疫聚焦抑制实验中均表现出中和hav的活性，且中和活性与其亲和力呈正相关。交叉竞争结合分析表明，HA6和HA9识别广泛重叠的表位，这些表位与HA1和HA12的表位重叠，尽管HA1和HA12识别不同的表位。此外，与已知的中和小鼠单克隆抗体的竞争分析表明，四种人单克隆抗体的表位与B5B3和K34C8的表位广泛重叠，这两种表位不同，但位于HAV衣壳上的单一免疫优势中和位点。具有较高亲和力的人单克隆抗体（HA6和HA9）可用于HAV感染的免疫预防。(C) 2003 Elsevier Inc.版权所有。
Four human monoclonal antibodies (MAbs) to hepatitis A virus (HAV) were isolated from a phage-displayed antibody library constructed from the peripheral blood lymphocytes (PBLs) of HAV-immune donors. The four MAbs showed differences in their affinity: two (HA6, HA9) of them were dominant after four rounds of panning, and showed higher affinity than the other two (HA1, HA12). All four MAbs showed HAV-neutralizing activity in radioimmunofocus inhibition assay and their neutralizing activity was positively correlated with their affinities. Analysis of their epitope specificity by cross-competition binding assays suggested that HA6 and HA9 recognize extensively overlapping epitopes, which overlap with those of HA1 and HA12, although HA1 and HA12 recognize distinct epitopes. In addition, competition assays with known neutralizing murine MAbs suggested that the epitopes of four human MAbs extensively overlap with those of B5B3 and K34C8 which are distinct but reside within the single, immunodominant neutralization site on the HAV capsid. The human MAbs (HA6 and HA9) with highest affinity may be useful in the immunoprophylaxis of HAV infection. (C) 2003 Elsevier Inc. All rights reserved.