Self-destructing Salmonella via temperature induced gene E of phage PhiX174 improves influenza HA DNA vaccine immune protection against H1N1 infection in mice model

The delivery of DNA vaccines is the principle impediment for implementation of DNA vaccination on a mass scale. In this study, we report a temperature induced conditionally expressed phage PhiX174 gene E mediated lysis of Salmonella under in vivo conditions that can increase the immunogenicity of a DNA vaccine delivered via Salmonella carrier system. We electroporated gene E encoding lysis plasmid pJHL187 along with the pcDNA-HA plasmid encoding H1N1 HA into attenuated Salmonella Typhimurium, strain JOL1893. Using C57BL/6 mice as the model, we showed that the mice intragastrically vaccinated with JOL1893 induced significant production of HA-specific humoral and cell mediated immune responses compared to the JOL1837, which carry pcDNA-HA plasmid alone. Furthermore, mice vaccinated with JOL1893 vaccine were fully protected against the lethal H1N1 challenge compared to the JOL1837 strain, which showed 90% protection only. However, none of the animals survived treated with either the PBS or the Salmonella carrying empty vector. Taken together, our results indicate that mucosal immunization with conditional lysis enabled live attenuated S. Typhimurium as a DNA vaccine carrier can induce efficient systemic and mucosal immune responses, and improves immune protection against a highly pathogenic H1N1 infection in mice model.