Antiviral Immune Responses Against Murine Cytomegalovirus Induced by an Oral Salmonella-Based Vaccine Expressing Viral M33 Protein

Human cytomegalovirus (CMV) is the leading cause of congenital infections, often leading to mental retardation and neurological disorders. It is a major public health priority to develop a vaccine for preventing and controlling human CMV infection. In this report, we generated an oral <i>Salmonella</i>-based vaccine to express the M33 protein of murine cytomegalovirus (MCMV) and investigated the anti-MCMV immune responses induced in mice immunized with this vaccine. Compared to those administered with phosphate-buffered saline (PBS) or a control vaccine without M33 expression, mice immunized with the vaccine expressing the M33 protein exhibited a remarkable induction of antiviral serum IgG and mucosal IgA humoral responses and a significant elicitation of antiviral T cell responses. Successful inhibition of viral growth in lungs, spleens, livers, and salivary glands was also found in the vaccinated animals compared to the PBS-treated animals or those immunized with the control vaccine without M33 expression. Furthermore, substantial protection against MCMV challenge was observed in mice immunized with the vaccine. Thus, <i>Salmonella</i>-based vaccine expressing MCMV M33 can induce anti-MCMV effective immune responses and protection. Our study implies that attenuated <i>Salmonella</i> expressing human CMV antigens, including its homologue to M33, may represent promising oral anti-CMV vaccine candidates.