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Next generation vaccine platform: polymersomes as stable nanocarriers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine
bioRxiv - Immunology Pub Date : 2021-01-25 , DOI: 10.1101/2021.01.24.427729
Jian Hang Lam , Amit Kumar Khan , Thomas Andrew Cornell , Regine Josefine Dress , Teck Wan Chia , Wen Wang William Yeow , Nur Khairiah Mohd-Ismail , Shrinivas Venkatraman , Kim Tien Ng , Yee-Joo Tan , Danielle E. Anderson , Florent Ginhoux , Madhavan Nallani

Multiple successful vaccines against SARS-CoV-2 are urgently needed to address the ongoing Covid-19 pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising of polybutadiene-b-polyethylene glycol and a cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells, which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of memory CD4+ and CD8+ T cells that produce Th1 cytokines. This study is an important step towards the development of an efficacious vaccine in humans.

中文翻译:

下一代疫苗平台:多聚体作为稳定的纳米载体,用于高度免疫原性和持久性的SARS-CoV-2穗状蛋白亚基疫苗

迫切需要针对SARS-CoV-2的多种成功疫苗,以解决持续进行的Covid-19大流行。在本工作中,我们描述了基于SARS-CoV-2穗蛋白与CpG佐剂共同施用的亚单位疫苗。为了增强我们制剂的免疫原性,抗原和佐剂都用我们专有的人工细胞膜(ACM)多聚体技术封装。从结构上讲,ACM聚合物囊泡是由两亲嵌段共聚物组成的自组装纳米囊泡,该两亲嵌段共聚物包含聚丁二烯-b-聚乙二醇和阳离子脂质1,2-二油酰基-3-三甲基铵-丙烷。在功能上,ACM聚合物囊泡可作为传递载体,被树突状细胞有效吸收,而树突状细胞是适应性免疫反应的关键引发剂。两剂我们的制剂在C57BL / 6小鼠中引起至少40天的稳固中和效价。此外,我们证实了产生Th1细胞因子的记忆CD4 +和CD8 + T细胞的存在。这项研究是开发有效疫苗的重要一步。
更新日期:2021-01-26
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