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

• DOI: 10.1016/j.biomaterials.2022.121907
• Publication Date: 2022-11-18T13:43:14Z
• Authors: 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; Shan Guan
• Keywords: DNA vaccine; 0301 basic medicine; SARS-CoV-2; [SDV]Life Sciences [q-bio]; Vaccination; COVID-19; DNA; Mucosal vaccine; Antibodies, Viral; Nonviral delivery system; Antibodies, Neutralizing; Article; 3. Good health; [SDV] Life Sciences [q-bio]; Mice; 03 medical and health sciences; SARS-CoV-2.; Vaccines, DNA; Animals; Nanoparticles; Pulmonary delivery; Peptides

AbstractThe 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.