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酵母表达的 H1 抗原免疫小鼠后产生的高滴度中和抗 H1N1 流感病毒抗体:一种有前途的流感疫苗候选物。

High-Titre Neutralizing Antibodies to H1N1 Influenza Virus after Mouse Immunization with Yeast Expressed H1 Antigen: A Promising Influenza Vaccine Candidate.

机构信息

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106 Warsaw, Poland.

Institute of Chemistry, University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland.

出版信息

J Immunol Res. 2019 Jan 8;2019:2463731. doi: 10.1155/2019/2463731. eCollection 2019.

Abstract

H1N1 influenza virus is still regarded as a serious pandemic threat. The most effective method of protection against influenza virus and the way to reduce the risk of epidemic or pandemic spread is vaccination. Influenza vaccine manufactured in a traditional way, though well developed, has some drawbacks and limitations which have stimulated interest in developing alternative approaches. In this study, we demonstrate that the recombinant H1 vaccine based on the hydrophilic haemagglutinin (HA) domain and produced in the yeast system elicited high titres of serum haemagglutination-inhibiting antibodies in mice. Transmission electron microscopy showed that H1 antigen oligomerizes into functional higher molecular forms similar to rosette-like structures. Analysis of the N-linked glycans using mass spectrometry revealed that the H1 protein is glycosylated at the same sites as the native HA. The recombinant antigen was secreted into a culture medium reaching approximately 10 mg/l. These results suggest that H1 produced in can be considered as the vaccine candidate against H1N1 virus.

摘要

H1N1 流感病毒仍然被认为是一种严重的大流行威胁。预防流感病毒的最有效方法,也是减少疫情或大流行传播风险的方法,是接种疫苗。传统方法制造的流感疫苗虽然已经很成熟,但存在一些缺点和局限性,这激发了人们对开发替代方法的兴趣。在这项研究中,我们证明了基于亲水性血凝素(HA)结构域的重组 H1 疫苗在酵母系统中产生,可在小鼠中引发高滴度的血清血凝抑制抗体。透射电子显微镜显示,H1 抗原聚合成类似于玫瑰花结样结构的功能性高分子形式。使用质谱法分析 N 连接聚糖表明,H1 蛋白在与天然 HA 相同的位点上发生糖基化。重组抗原分泌到培养基中,达到约 10mg/L。这些结果表明,可以将在 中产生的 H1 视为针对 H1N1 病毒的候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5285/6341273/cc661ec9b2b7/JIR2019-2463731.001.jpg

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