Intranasal G5-BGG/pDNA vaccine elicits protective systemic and mucosal immunity against SARS-CoV-2 by transfecting mucosal dendritic cells

Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines that provide both disease protection and transmission inhibition. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal-associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5-BGG and antigen-expressing plasmid DNA (pSP), named G5-BGG/pSP complex, was developed to activate NALT and to promote both systemic and mucosal immune defense. It was found that G5-BGG/pSP could traverse mucosal barriers and deliver DNA to the target cells because of its superior nasal retention and permeability characteristics. The intranasal G5-BGG/pSP complex elicited robust antigen-specific immune responses, such as the notable production of IgG antibody against several severe acute respiratory syndrome coronavirus 2 variants. More importantly, it induced elevated levels of antigen-specific IgA antibody and a significant expansion of the lung-resident T lymphocyte population in the respiratory tract. Notably, the intranasal G5-BGG/pSP complex resulted in antigen expression and maturation of dendritic cells in nasal mucosae, suggesting that it is a feasible pathway for initiating immune responses. These findings exhibited the potential of G5-BGG, a novel cationic material, as an effective gene carrier for intranasal vaccines to obtain robust systemic and mucosal immunity. This article is protected by copyright. All rights reserved