Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge
Brief intro:
- Author: 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
- Journal: Biomaterials
- Doi: https://www.doi.org/10.1016/j.biomaterials.2022.121907
- Publication Date: 2022 Nov 18
Products/Services used in the paper
Quotation shows PackGene: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.
Research Field:Covid-related
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.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
