Polymersomes as Stable Nanocarriers for a Highly Immunogenic and Durable SARS-CoV-2 Spike Protein Subunit Vaccine,ACS Nano

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Polymersomes as Stable Nanocarriers for a Highly Immunogenic and Durable SARS-CoV-2 Spike Protein Subunit Vaccine
ACS Nano ( IF 15.8 ) Pub Date : 2021-10-07 , DOI: 10.1021/acsnano.1c01243
Jian Hang Lam ₁ , Amit K Khan ₁ , Thomas A Cornell ₁ , Teck Wan Chia ₁ , Regine J Dress ₂ , Wen Wang William Yeow ₁ , Nur Khairiah Mohd-Ismail ₃ , Shrinivas Venkataraman ₁ , Kim Tien Ng ₃ , Yee-Joo Tan _{3,

4} , Danielle E Anderson ₅ , Florent Ginhoux _{2,

6} , Madhavan Nallani ₁

Affiliation

Multiple successful vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to address the ongoing coronavirus disease 2019 (Covid-19) pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein coadministered 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 poly(butadiene)-b-poly(ethylene 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 (DC1 and DC2), which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing antibody titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of functional memory CD4⁺ and CD8⁺ T cells that produce T helper type 1 cytokines. This study is an important step toward the development of an efficacious vaccine in humans.

中文翻译：

聚合物囊泡作为高免疫原性和耐用的 SARS-CoV-2 刺突蛋白亚基疫苗的稳定纳米载体

迫切需要针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的多种成功疫苗来应对持续的 2019 年冠状病毒病 (Covid-19) 大流行。在目前的工作中，我们描述了一种基于 SARS-CoV-2 刺突蛋白与 CpG 佐剂共同给药的亚单位疫苗。为了增强我们制剂的免疫原性，抗原和佐剂均采用我们专有的人工细胞膜 (ACM) 聚合物囊泡技术进行封装。在结构上，ACM聚合物囊泡是由包含聚（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-丙烷的两亲性嵌段共聚物组成的自组装纳米级囊泡。从功能上讲，ACM 聚合物囊泡可作为递送载体，被树突状细胞（DC1 和 DC2）有效吸收，而树突状细胞是适应性免疫反应的关键启动子。我们的制剂的两个剂量在 C57BL/6 小鼠中引发了强大的中和抗体滴度，该滴度持续至少 40 天。^{此外，我们确认了功能性记忆 CD4 +}和 CD8 ⁺ T 细胞的存在，它们产生 1 型辅助 T 细胞因子。这项研究是开发人类有效疫苗的重要一步。

更新日期：2021-10-26

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