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生产和纯化携带流感病毒 LAH 结构域的嵌合 HBc 病毒样颗粒作为疫苗候选物。

Production and purification of chimeric HBc virus-like particles carrying influenza virus LAH domain as vaccine candidates.

机构信息

Latvian Biomedical Research and Study Centre, Ratsupites 1, Riga, LV-1067, Latvia.

Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg.

出版信息

BMC Biotechnol. 2017 Nov 10;17(1):79. doi: 10.1186/s12896-017-0396-8.

DOI:10.1186/s12896-017-0396-8
PMID:29126399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5681787/
Abstract

BACKGROUND

The lack of a universal influenza vaccine is a global health problem. Interest is now focused on structurally conserved protein domains capable of eliciting protection against a broad range of influenza virus strains. The long alpha helix (LAH) is an attractive vaccine component since it is one of the most conserved influenza hemagglutinin (HA) stalk regions. For an improved immune response, the LAH domain from H3N2 strain has been incorporated into virus-like particles (VLPs) derived from hepatitis B virus core protein (HBc) using recently developed tandem core technology.

RESULTS

Fermentation conditions for recombinant HBc-LAH were established in yeast Pichia pastoris and a rapid and efficient purification method for chimeric VLPs was developed to match the requirements for industrial scale-up. Purified VLPs induced strong antibody responses against both group 1 and group 2 HA proteins in mice.

CONCLUSION

Our results indicate that the tandem core technology is a useful tool for incorporation of highly hydrophobic LAH domain into HBc VLPs. Chimeric VLPs can be successfully produced in bioreactor using yeast expression system. Immunologic data indicate that HBc VLPs carrying the LAH antigen represent a promising universal influenza vaccine component.

摘要

背景

缺乏通用流感疫苗是一个全球性的健康问题。目前的研究重点集中在能够针对广泛的流感病毒株产生保护作用的结构保守的蛋白质结构域上。长α螺旋（LAH）是一种有吸引力的疫苗成分，因为它是流感血凝素（HA）茎区最保守的区域之一。为了提高免疫反应，已将来自 H3N2 株的 LAH 结构域通过最近开发的串联核心技术纳入乙型肝炎病毒核心蛋白（HBc）衍生的病毒样颗粒（VLPs）中。

结果

在毕赤酵母中建立了重组 HBc-LAH 的发酵条件，并开发了一种快速高效的嵌合 VLPs 纯化方法，以满足工业规模扩大的要求。纯化的 VLPs 在小鼠中诱导了针对第 1 组和第 2 组 HA 蛋白的强烈抗体反应。

结论

我们的结果表明，串联核心技术是将高度疏水性的 LAH 结构域纳入 HBc VLPs 的有用工具。可以使用酵母表达系统在生物反应器中成功生产嵌合 VLPs。免疫数据表明，携带 LAH 抗原的 HBc VLPs 是一种有前途的通用流感疫苗成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/fd74e108efd8/12896_2017_396_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/7f85c3c163f4/12896_2017_396_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/ba53fdc2c8cc/12896_2017_396_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/4865116fbcb8/12896_2017_396_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/9edef7f43dee/12896_2017_396_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/c645814336a6/12896_2017_396_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/af3aaca81038/12896_2017_396_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/fd74e108efd8/12896_2017_396_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/7f85c3c163f4/12896_2017_396_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/ba53fdc2c8cc/12896_2017_396_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/4865116fbcb8/12896_2017_396_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/9edef7f43dee/12896_2017_396_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/c645814336a6/12896_2017_396_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/af3aaca81038/12896_2017_396_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8af9/5681787/fd74e108efd8/12896_2017_396_Fig7_HTML.jpg

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