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开发具有内在免疫刺激特性的病毒样颗粒作为候选疫苗。

Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates.

作者信息

Collett Simon, Earnest Linda, Carrera Montoya Julio, Edeling Melissa A, Yap Ashley, Wong Chinn Yi, Christiansen Dale, Roberts Jason, Mumford Jamie, Lecouturier Valerie, Pavot Vincent, Marco Sergio, Loi Joon Keit, Simmons Cameron, Gulab Shivali A, Mackenzie Jason M, Elbourne Aaron, Ramsland Paul A, Cameron Garth, Hans Dhiraj, Godfrey Dale I, Torresi Joseph

机构信息

School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, VIC, Australia.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia.

出版信息

Front Microbiol. 2023 Jun 7;14:1065609. doi: 10.3389/fmicb.2023.1065609. eCollection 2023.


DOI:10.3389/fmicb.2023.1065609
PMID:37350788
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10282183/
Abstract

The development of virus-like particle (VLP) based vaccines for human papillomavirus, hepatitis B and hepatitis E viruses represented a breakthrough in vaccine development. However, for dengue and COVID-19, technical complications, such as an incomplete understanding of the requirements for protective immunity, but also limitations in processes to manufacture VLP vaccines for enveloped viruses to large scale, have hampered VLP vaccine development. Selecting the right adjuvant is also an important consideration to ensure that a VLP vaccine induces protective antibody and T cell responses. For diseases like COVID-19 and dengue fever caused by RNA viruses that exist as families of viral variants with the potential to escape vaccine-induced immunity, the development of more efficacious vaccines is also necessary. Here, we describe the development and characterisation of novel VLP vaccine candidates using SARS-CoV-2 and dengue virus (DENV), containing the major viral structural proteins, as protypes for a novel approach to produce VLP vaccines. The VLPs were characterised by Western immunoblot, enzyme immunoassay, electron and atomic force microscopy, and and immunogenicity studies. Microscopy techniques showed proteins self-assemble to form VLPs authentic to native viruses. The inclusion of the glycolipid adjuvant, α-galactosylceramide (α-GalCer) in the vaccine formulation led to high levels of natural killer T (NKT) cell stimulation , and strong antibody and memory CD8 T cell responses , demonstrated with SARS-CoV-2, hepatitis C virus (HCV) and DEN VLPs. This study shows our unique vaccine formulation presents a promising, and much needed, new vaccine platform in the fight against infections caused by enveloped RNA viruses.

摘要

基于病毒样颗粒(VLP)的人乳头瘤病毒、乙型肝炎病毒和戊型肝炎病毒疫苗的研发代表了疫苗研发领域的一项突破。然而,对于登革热和新冠病毒疾病,技术难题,比如对保护性免疫要求的认识不全面,以及大规模生产包膜病毒VLP疫苗过程中的局限性,都阻碍了VLP疫苗的研发。选择合适的佐剂也是确保VLP疫苗诱导保护性抗体和T细胞反应的一项重要考量。对于像新冠病毒疾病和登革热这样由RNA病毒引起的疾病,这些病毒以病毒变种家族的形式存在,有可能逃避疫苗诱导的免疫,因此研发更有效的疫苗也很有必要。在此,我们描述了以严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和登革热病毒(DENV)为原型,使用包含主要病毒结构蛋白的新型VLP候选疫苗的研发与特性分析,这是一种生产VLP疫苗的新方法。通过蛋白质免疫印迹法、酶免疫测定法、电子显微镜和原子力显微镜以及免疫原性研究对这些VLP进行了特性分析。显微镜技术显示蛋白质自组装形成了与天然病毒一致的VLP。在疫苗制剂中加入糖脂佐剂α-半乳糖神经酰胺(α-GalCer)可导致高水平的自然杀伤T(NKT)细胞刺激,并引发强烈的抗体和记忆性CD8 T细胞反应,这在SARS-CoV-2、丙型肝炎病毒(HCV)和登革热病毒VLP中得到了证实。这项研究表明,我们独特的疫苗制剂在对抗包膜RNA病毒引起的感染方面呈现出一个有前景且急需的新疫苗平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/f98f9e00b838/fmicb-14-1065609-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/561fad9965ad/fmicb-14-1065609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/e0bcdd508ce2/fmicb-14-1065609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/7d2ff2eedb1e/fmicb-14-1065609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/98971e9f4dee/fmicb-14-1065609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/1cab6e4be75b/fmicb-14-1065609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/01f3cfd42b68/fmicb-14-1065609-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/9911c9290659/fmicb-14-1065609-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/f094f60aa6b0/fmicb-14-1065609-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/dac24c06f954/fmicb-14-1065609-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/636c50a64a29/fmicb-14-1065609-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/02e128008ccb/fmicb-14-1065609-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/f98f9e00b838/fmicb-14-1065609-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/561fad9965ad/fmicb-14-1065609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/e0bcdd508ce2/fmicb-14-1065609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/7d2ff2eedb1e/fmicb-14-1065609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/98971e9f4dee/fmicb-14-1065609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/1cab6e4be75b/fmicb-14-1065609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/01f3cfd42b68/fmicb-14-1065609-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/9911c9290659/fmicb-14-1065609-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/f094f60aa6b0/fmicb-14-1065609-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/dac24c06f954/fmicb-14-1065609-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/636c50a64a29/fmicb-14-1065609-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/02e128008ccb/fmicb-14-1065609-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f3/10282183/f98f9e00b838/fmicb-14-1065609-g012.jpg

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