Biomaterials. 2022 Nov 18
Si Sun, Entao Li, Gan Zhao, Jie Tang, Qianfei Zuo, Larry Cai, Chuanfei Xu, Cheng Sui, Yangxue Ou, Chang Liu, Haibo Li, Yuan Ding, Chao Li, Dongshui Lu, Weijun Zhang, Ping Luo, Ping Cheng, Yuwei Gao, Changchun Tu, Bruno Pitard, Joseph Rosenecker, Bin Wang, Yan Liu, Quanming Zou, and Shan Guana
Products used in the paper Details Operation
ACE2-293T cells; Luc-SARS-Cov-917 2 pseudotyped virus ACE2-293T cells (ACE2-expressing cell line, constructed by hygromycin B screening) were purchased from PackGene (LV-2058, Guangzhou, China). Serum or BALF were incubated with 10 μl of Luc-SARS-Cov-917 2 pseudotyped virus (LV-2058, PackGene, China) for 60 min, then added to the HEK293T 918 cells stably expressing ACE2 to incubate in a standard incubator (37℃, 5% CO2) for 72 h. Request Quote

Research Field: Covid-related

Keywords: Mucosal vaccine, SARS-CoV-2, DNA vaccine, Pulmonary delivery, Nonviral delivery system

Abstract

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 protective 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 pulmonary 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 immunity against SARS-CoV-2.

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