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

Si Sun,Entao Li,Gan Zhao,Jie Tang,Qianfei Zuo,L. Cai,Chuanfei Xu,Cheng Sui,Yangxue Ou,Chang Liu,Haibo Li,Yuan Ding,Chao Li,D. Lu,Wei-jun Zhang,P. Luo,Ping Cheng,Yuwei Gao,C. Tu,B. Pitard,J. Rosenecker,Bin Wang,Y. Liu,Quanming Zou,S. Guan

Published 2022 in bioRxiv

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 the 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). Not only displays the pSpike/PP-sNp superior gene-transfection and favorable biocompatibility in the mouse airway, but pSpike/PP-sNp 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, 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 might be a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.

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