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可中和甲型流感病毒H5N1亚型同源和异源毒株及分支的人源单链抗体。

Human single-chain antibodies that neutralize homologous and heterologous strains and clades of influenza A virus subtype H5N1.

作者信息

Maneewatch Santi, Thanongsaksrikul Jeeraphong, Songserm Thaweesak, Thueng-In Kanyarat, Kulkeaw Kasem, Thathaisong Umaporn, Srimanote Potjanee, Tongtawe Pongsri, Tapchaisri Pramuan, Chaicumpa Wanpen

机构信息

Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Antivir Ther. 2009;14(2):221-30.

Abstract

BACKGROUND

Human antibodies that interfere with the biological activity of haemagglutinins (HAs) of influenza viruses have high potential as an antiviral agent.

METHODS

Human single-chain antibody fragments (HuScFv) to recombinant and native HAs of the influenza virus H5N1 subtype were produced using a human antibody phage display library with the intention to increase the therapeutic arsenal against this highly pathogenic virus.

RESULTS

The HuScFv inhibited HA activity and neutralized infectivity of both homologous and heterologous strains and clades of the H5N1 subtype in Madin-Darby canine kidney cell cultures. Intraperitoneally injected HuScFv also mediated immunotherapeutic protection in mice that were intranasally challenged with highly pathogenic H5N1 viruses belonging to different strains and clades.

CONCLUSIONS

Our data indicate that it might be worth pursuing these HuScFv further for future consideration as candidates for influenza intervention and treatment.

摘要

背景

干扰流感病毒血凝素(HA)生物活性的人源抗体具有很高的抗病毒潜力。

方法

利用人源抗体噬菌体展示文库制备针对重组和天然H5N1亚型流感病毒HA的人源单链抗体片段(HuScFv),旨在增加针对这种高致病性病毒的治疗手段。

结果

HuScFv在Madin-Darby犬肾细胞培养物中抑制了HA活性,并中和了H5N1亚型同源和异源毒株及分支的感染性。腹腔注射的HuScFv还介导了对经鼻感染不同毒株和分支的高致病性H5N1病毒的小鼠的免疫治疗保护作用。

结论

我们的数据表明,进一步研究这些HuScFv作为流感干预和治疗候选药物可能是值得的。

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