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The emerging SARS\u2010CoV\u20102 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\u2010deficient type\u20105 adenoviral vaccine with a built\u2010in double\u2010strand RNA adjuvant and the vaccine expresses the SARS\u2010CoV\u20102 Omicron BA.1 spike (S) antigen (hereinafter referred to as \u201cthe oral vaccine\u201d). We found that two doses of the oral vaccine in BALB\/c mice generated long\u2010lasting S\u2010specific 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.<\/jats:p>","DOI":"10.1002\/jmv.70236","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T02:50:52Z","timestamp":1739501452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral Ad5 Vector\u2010Based SARS\u2010CoV\u20102 Vaccine Effectively Induces Mucosal and Systemic Immune Responses in BALB\/c Mice"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9639-5607","authenticated-orcid":false,"given":"Tongyao","family":"Mao","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention 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