An Oral Vaccine Derived from Attenuated Salmonella Producing Murine Cytomegalovirus M24 Protein Induces Successful Antiviral Immune Responses in Mice

<p><strong>Background:</strong> Oral gene delivery vectors, such as those derived from attenuated <em>Salmonella</em> strains, have shown great promise in oral vaccine development against various human diseases. Human cytomegalovirus (CMV) is a herpesvirus capable of affecting the global population and establishing lifelong infection. Generation of an anti-CMV vaccine is a major public health priority. <strong>Methods:</strong> This study reports the development of a novel weakened <em>Salmonella</em> strain, S713, and the effects of this strain as an oral vaccine candidate against murine cytomegalovirus (MCMV) infection in mice. <strong>Results:</strong> The weakened <em>Salmonella</em> strain S713 was attenuated in killing mice in vivo by &gt;500,000 fold compared to a clinical strain, following intragastric instillation in animals. Mice intragastrically immunized with S713 that produced MCMV M24 protein exhibited elevated anti-MCMV mucosal IgA and serum IgG titers and enhanced anti-MCMV T cell responses. Moreover, immunization with the generated vaccine in MCMV-challenged mice not only suppressed viral replication in lungs, spleens, livers, and salivary glands but also increased animal survival. <strong>Conclusions:</strong> These findings demonstrate strong and effective anti-MCMV immune responses induced by the generated M24-expressing vaccine. Furthermore, our results reveal the promising capability of weakened strain S713 expressing different CMV proteins to act as oral vaccines against CMV infections and diseases.</p>