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嵌合病毒样颗粒共展示血凝素茎部和 DnaK 的 C 末端片段在小鼠中赋予异源流感保护。

Chimeric Virus-like Particles Co-Displaying Hemagglutinin Stem and the C-Terminal Fragment of DnaK Confer Heterologous Influenza Protection in Mice.

机构信息

Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China.

College of Life Sciences, Hunan Normal University, Changsha 410082, China.

出版信息

Viruses. 2022 Sep 23;14(10):2109. doi: 10.3390/v14102109.

DOI:10.3390/v14102109
PMID:36298664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9610613/
Abstract

Influenza virus hemagglutinin (HA) stem is currently regarded as an extremely promising immunogen for designing universal influenza vaccines. The appropriate antigen-presenting vaccine vector would be conducive to increasing the immunogenicity of the HA stem antigen. In this study, we generated chimeric virus-like particles (cVLPs) co-displaying the truncated C-terminal of DnaK from and H1 stem or full-length H1 antigen using the baculovirus expression system. Transmission electronic micrography revealed the expression and presentation of H1 stem antigens on the surface of VLPs. Vaccinations of mice with the H1 stem cVLPs induced H1-specific immune responses and provided heterologous immune protection in vivo, which was more effective than vaccinations with VLPs displaying H1 stem alone in protecting mice against weight loss as well as increasing survival rates after lethal influenza viral challenge. The results indicate that the incorporation of the truncated C-terminal of DnaK as an adjuvant protein into the cVLPs significantly enhances the H1-specific immunity and immune protection. We have explicitly identified the VLP platform as an effective way of expressing HA stem antigen and revealed that chimeric VLP is an vaccine vector for developing HA stem-based universal influenza vaccines.

摘要

流感病毒血凝素（HA）茎目前被认为是设计通用流感疫苗的极有前途的免疫原。适当的抗原呈递疫苗载体将有利于提高 HA 茎抗原的免疫原性。在这项研究中，我们使用杆状病毒表达系统生成了共展示来自 和 H1 茎或全长 H1 抗原的截断 C 端的嵌合病毒样颗粒（cVLPs）。透射电子显微镜显示 VLPs 表面表达和呈现 H1 茎抗原。用 H1 茎 cVLPs 免疫小鼠可诱导 H1 特异性免疫应答，并在体内提供异源免疫保护，这比单独用 VLPs 显示 H1 茎更有效地保护小鼠免受体重减轻，并提高在致命流感病毒攻击后的存活率。结果表明，将截断的 DnaK C 端作为佐剂蛋白掺入 cVLPs 可显著增强 H1 特异性免疫和免疫保护。我们明确将 VLP 平台鉴定为表达 HA 茎抗原的有效方法，并揭示嵌合 VLP 是开发基于 HA 茎的通用流感疫苗的疫苗载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/beb697527e7b/viruses-14-02109-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/cc571dacbaec/viruses-14-02109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/fb18591e1b3d/viruses-14-02109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/0ea0f9dc4820/viruses-14-02109-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/652347de43cb/viruses-14-02109-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/063f35f3ef48/viruses-14-02109-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/2ef3444f5efe/viruses-14-02109-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/beb697527e7b/viruses-14-02109-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/cc571dacbaec/viruses-14-02109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/fb18591e1b3d/viruses-14-02109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/0ea0f9dc4820/viruses-14-02109-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/652347de43cb/viruses-14-02109-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/063f35f3ef48/viruses-14-02109-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/2ef3444f5efe/viruses-14-02109-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7876/9610613/beb697527e7b/viruses-14-02109-g007.jpg

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