Intranasal G5‐BGG/pDNA Vaccine Elicits Protective Systemic and Mucosal Immunity against SARS‐CoV‐2 by Transfecting Mucosal Dendritic Cells

Abstract Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines. 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, is developed to activate NALT and to promote both systemic and mucosal immune defense. 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 elicits robust antigen‐specific immune responses, such as the notable production of IgG antibody against several virus variants. More importantly, it induces elevated levels of antigen‐specific IgA antibody and a significant expansion of the lung‐resident T lymphocyte population. Notably, the intranasal G5‐BGG/pSP complex results in antigen expression and maturation of dendritic cells in nasal mucosae. These findings exhibit the potential of G5‐BGG, a novel cationic material, as an effective gene carrier for intranasal vaccines to obtain robust systemic and mucosal immunity.