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一种新型聚合物纳米粒子聚二甲基二烯丙基氯化铵作为佐剂增强了 SARS-CoV-2 亚单位疫苗的免疫反应。

A Novel Polymer Nanoparticle Polydimethyl Diallyl Ammonium Chloride as An Adjuvant Enhances the Immune Response of SARS-CoV-2 Subunit Vaccine.

机构信息

School of Pharmacy, Nanjing Tech University, Nanjing, 211816, China.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing, 210014, China.

出版信息

Adv Healthc Mater. 2024 Jun;13(15):e2304575. doi: 10.1002/adhm.202304575. Epub 2024 Mar 10.

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has a significant impact on global health and the economy. It has underscored the urgent need for a stable, easily produced and effective vaccine. This study presents a novel approach using SARS-CoV-2 spike (S) protein-conjugated nanoparticles (NPs) in combination with cyclic GMP-AMP (cGAMP) (S-NPs-cGAMP) as a subunit vaccine. When mice are immunized, the antiserum of S-NPs-cGAMP group exhibits a 16-fold increase in neutralizing activity against a pseudovirus, compared to S protein group. Additionally, S-NPs-cGAMP induces even higher levels of neutralizing antibodies. Remarkably, the vaccine also triggers a robust humoral immune response, as evidenced by a notable elevation in virus-specific IgG and IgM antibodies. Furthermore, after 42 days of immunization, there is an observed increase in specific immune cell populations in the spleen. CD3CD4 and CD3CD8T lymphocytes, as well as B220CD19 and CD3CD49b NK lymphocytes, show an upward trend, indicating a positive cellular immune response. Moreover, the S-NPs-cGAMP demonstrates promising results against the Delta strain and exhibits good cross-neutralization potential against other variants. These findings suggest that pDMDAAC NPs is potential adjuvant and could serve as a versatile platform for future vaccine development.

摘要

新型冠状病毒病(COVID-19)大流行是由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的,对全球健康和经济产生了重大影响。它突显了对稳定、易于生产和有效的疫苗的迫切需求。本研究提出了一种使用 SARS-CoV-2 刺突(S)蛋白缀合纳米颗粒(NPs)与环二核苷酸(cGAMP)(S-NPs-cGAMP)联合作为亚单位疫苗的新方法。当用小鼠进行免疫时,与 S 蛋白组相比,S-NPs-cGAMP 组的抗血清对假病毒的中和活性增加了 16 倍。此外,S-NPs-cGAMP 还诱导更高水平的中和抗体。值得注意的是,该疫苗还引发了强烈的体液免疫反应,表现为病毒特异性 IgG 和 IgM 抗体的显著升高。此外,在免疫 42 天后,脾脏中观察到特定免疫细胞群体的增加。CD3CD4 和 CD3CD8T 淋巴细胞以及 B220CD19 和 CD3CD49b NK 淋巴细胞呈上升趋势,表明存在正向细胞免疫反应。此外,S-NPs-cGAMP 对 Delta 株显示出有希望的结果,并对其他变体表现出良好的交叉中和潜力。这些发现表明 pDMDAAC NPs 是一种有潜力的佐剂,并可能成为未来疫苗开发的多功能平台。

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