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

Background

Oral gene delivery vectors, such as those derived from attenuated Salmonella 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.

Methods

This study reports the development of a novel weakened Salmonella strain, S713, and the effects of this strain as an oral vaccine candidate against murine cytomegalovirus (MCMV) infection in mice.

Results

The weakened Salmonella strain S713 was attenuated in killing mice in vivo by >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.

Conclusions

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.