Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge

文献类型： 外文期刊

第一作者： Sun, Si

作者： Sun, Si;Zuo, Qianfei;Xu, Chuanfei;Ou, Yangxue;Liu, Chang;Li, Haibo;Li, Chao;Lu, Dongshui;Zhang, Weijun;Luo, Ping;Cheng, Ping;Zou, Quanming;Guan, Shan;Gao, Yuwei;Tu, Changchun;Liu, Yan;Zhao, Gan;Sui, Cheng;Ding, Yuan;Wang, Bin;Tang, Jie;Cai, Larry;Pitard, Bruno;Rosenecker, Joseph;Wang, Bin;Wang, Bin;Liu, Yan;Zou, Quanming;Guan, Shan

作者机构：

关键词： Mucosal vaccine; SARS-CoV-2; DNA vaccine; Pulmonary delivery; Nonviral delivery system

期刊名称：BIOMATERIALS （ 影响因子：15.304； 五年影响因子：14.431 ）

ISSN： 0142-9612

年卷期： 2023 年 292 卷

页码：

收录情况： SCI

摘要： The ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer pro-tective immune responses against SARS-CoV-2 challenge due to insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pul-monary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). The pSpike/PP-sNp not only displays superior gene transfection and favorable biocompatibility in the mouse airway, but also promotes a tripartite immunity consisting of systemic, cellular, and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, immunization with pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp is a promising platform in mediating DNA vaccines to elicit all-around mucosal im-munity against SARS-CoV-2.

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