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甲型 H1N1 流感病毒血凝素茎部区域上的中和性单克隆抗体识别表位。

An epitope on the stem region of hemagglutinin of H1N1 influenza A virus recognized by neutralizing monoclonal antibody.

机构信息

Central Laboratory, Shaanxi Provincial People's Hospital, Xi'an, 710068, China; Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an, 710068, China.

Institute of Integrated Medicine, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.

出版信息

Biochem Biophys Res Commun. 2019 Oct 15;518(2):319-324. doi: 10.1016/j.bbrc.2019.08.055. Epub 2019 Aug 14.

Abstract

Influenza A viruses are a major threat to human health and inflict a significant public health challenge worldwide. Hemagglutinin (HA) is the main contributor to the infectivity of the virus and is a potential target for the development of antiviral therapeutic agents. The stem region of HA, which has been shown to be conserved, is the primary target in the development of antibody-based therapeutic strategies and preventive tools. Here, we confirmed the neutralizing activity and prophylactic efficacy of murine monoclonal antibody PR8-25 as well as Western blot analysis of different influenza virus strains. Then, we identified the epitope of PR8-25, 328-LRMVTGLRNIPS-339, by phage-displayed 12-mer random peptide library. The identified epitope targeted in the stem region of HA, specifically at the C-terminal of the HA1 fragment. This result suggest that the identified epitope may be a potential basis for antiviral drugs and stem-based universal influenza vaccines.

摘要

甲型流感病毒对人类健康构成重大威胁,在全球范围内造成重大公共卫生挑战。血凝素 (HA) 是病毒感染力的主要贡献者,也是开发抗病毒治疗药物的潜在目标。已经证明,HA 的茎区是保守的,是基于抗体的治疗策略和预防工具的主要目标。在这里,我们证实了鼠单克隆抗体 PR8-25 的中和活性和预防功效,以及对不同流感病毒株的 Western blot 分析。然后,我们通过噬菌体展示 12 肽随机肽文库鉴定了 PR8-25 的表位,328-LRMVTGLRNIPS-339。鉴定的表位针对 HA 的茎区,特别是在 HA1 片段的 C 末端。这一结果表明,鉴定的表位可能是抗病毒药物和基于茎的通用流感疫苗的潜在基础。

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