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植物中产生的链霉亲和素标记的禽流感血凝素的寡聚体引发中和免疫反应。

-Formulated Oligomers of Strep-Tagged Avian Influenza Haemagglutinin Produced in Plants Cause Neutralizing Immune Responses.

作者信息

Phan Hoang Trong, Gresch Ulrike, Conrad Udo

机构信息

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Seeland, Germany.

出版信息

Front Bioeng Biotechnol. 2018 Aug 20;6:115. doi: 10.3389/fbioe.2018.00115. eCollection 2018.

DOI:10.3389/fbioe.2018.00115
PMID:30177967
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6110258/
Abstract

The worldwide emergence of the novel influenza A H5N1 and H5N8 has notably and directly impacted the poultry industry, resulting in the need for effective and cheap vaccination strategies to protect poultry worldwide. Subunit vaccines from plants can be produced for a low cost, and plant production systems are easily scaled up at low infrastructure cost. However, subunit vaccines generally induce low immunogenicity against influenza. To address this issue, we present a new and innovative method to generate highly immunogenic H5 oligomers. The method is based on specific and high-affinity interaction between engineered streptavidin (Strep-Tactin® XT) and the Strep-tag II peptide. H5-Strep-tag II-tagged trimers were produced transient agroinfection in tobacco leaves and purified, and oligomers were formulated by adding purified homotetrameric Strep-Tactin® XT. Immunogenicity was tested by performing mouse immunizations. Haemagglutinin oligomers produced by combining Strep-Tactin® XT and Strep-tag II-fused haemagglutinin trimers from plants raised potentially neutralizing antibodies in mice. Vaccines based on actual H5N1 haemagglutinin can be produced by combining strep-tagged haemagglutinin trimers from plants and Strep-Tactin® XT.

摘要

新型甲型H5N1和H5N8流感病毒在全球范围内的出现对家禽业产生了显著且直接的影响，这就需要有有效且廉价的疫苗接种策略来保护全球的家禽。植物源亚单位疫苗能够低成本生产，并且植物生产系统易于以较低的基础设施成本进行扩大规模。然而，亚单位疫苗通常对流感的免疫原性较低。为了解决这个问题，我们提出了一种全新的创新方法来生成高免疫原性的H5寡聚体。该方法基于工程化链霉亲和素（Strep-Tactin® XT）与链霉标签II肽之间的特异性高亲和力相互作用。带有H5-链霉标签II的三聚体通过在烟草叶片中进行瞬时农杆菌感染产生并纯化，然后通过添加纯化的同源四聚体Strep-Tactin® XT来制备寡聚体。通过对小鼠进行免疫接种来测试免疫原性。由Strep-Tactin® XT与来自植物的链霉标签II融合的血凝素三聚体组合产生的血凝素寡聚体在小鼠体内引发了潜在的中和抗体。基于实际H5N1血凝素的疫苗可以通过将来自植物的链霉标签化血凝素三聚体与Strep-Tactin® XT组合来生产。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/4afaf5c584ef/fbioe-06-00115-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/218b30abae75/fbioe-06-00115-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/8815f9117186/fbioe-06-00115-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/306c102e5d61/fbioe-06-00115-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/b63c175d876f/fbioe-06-00115-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/6b68ec5810fe/fbioe-06-00115-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/4afaf5c584ef/fbioe-06-00115-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/218b30abae75/fbioe-06-00115-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/8815f9117186/fbioe-06-00115-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/306c102e5d61/fbioe-06-00115-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/b63c175d876f/fbioe-06-00115-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/6b68ec5810fe/fbioe-06-00115-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb6/6110258/4afaf5c584ef/fbioe-06-00115-g0006.jpg

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