Oral vaccines have a distinctive advantage of stimulating immune responses in the mucosa, where numerous pathogens gain entry and cause disease. Although various efforts have been attempted to create recombinant mucosal vaccines that provoke strong immunogenicity, the outcomes in clinical trials have been weak or inconsistent. Therefore, next-generation mucosal vaccines are needed that are more immunogenic. Here, we discuss oral vaccines with an emphasis on a next-generation mucosal vaccine that utilizes a nonreplicating human recombinant adenovirus type-5 (rAd5) vector. Numerous positive clinical results investigating oral rAd5 vaccines are reviewed, with a summary of the immunogenicity and efficacy results for specific vaccine indications of influenza, norovirus, and SARS-CoV-2. The determination of correlates of protection for oral vaccination and the potential impact this novel vaccine formulation may have on disease transmission are also discussed. In summary, successful oral vaccination can be accomplished and would have major public health benefits if approved.

口服疫苗具有刺激粘膜免疫反应的独特优势，许多病原体可以进入粘膜并引起疾病。尽管已经尝试了各种努力来制造具有强免疫原性的重组粘膜疫苗，但临床试验的结果却很弱或不一致。因此，需要更具免疫原性的下一代粘膜疫苗。在这里，我们讨论口服疫苗，重点讨论利用非复制型人重组腺病毒 5 型 (rAd5) 载体的下一代粘膜疫苗。回顾了口服 rAd5 疫苗的大量积极临床结果，并总结了流感、诺如病毒和 SARS-CoV-2 特定疫苗适应症的免疫原性和功效结果。还讨论了口服疫苗接种保护相关性的确定以及这种新型疫苗制剂可能对疾病传播产生的潜在影响。总之，成功的口服疫苗接种是可以实现的，如果获得批准，将产生重大的公共健康益处。