Oral Ad5 Vector‐Based SARS‐CoV‐2 Vaccine Effectively Induces Mucosal and Systemic Immune Responses in BALB/c Mice

ABSTRACT Mucosal immunity is essential for preventing viral infections through the mucosal route. The emerging SARS‐CoV‐2 variants have posed additional hurdles to the efficiency of existing vaccines. The rapid development of novel vaccines that generate broad mucosal and systemic immunity could be the most effective strategy to address this issue. In this study, we developed a recombinant and replication‐deficient type‐5 adenoviral vaccine with a built‐in double‐strand RNA adjuvant and the vaccine expresses the SARS‐CoV‐2 Omicron BA.1 spike (S) antigen (hereinafter referred to as “the oral vaccine”). We found that two doses of the oral vaccine in BALB/c mice generated long‐lasting S‐specific mucosal and systemic immune responses, as well as broad neutralizing antibodies and SIgA antibodies. In addition, we found that compared to an mRNA vaccine booster, using the oral vaccine as a booster could induce both effective mucosal and systemic immunity, addressing the limitation of mRNA vaccines in eliciting mucosal immunity. Prospective oral vaccines require further investigation into development and potential applications, particularly viral challenge experiments, before clinical trials.