Salmonella is still one of the most important pathogens in humans throughout the world resulting in millions of infections and economic losses. Each year, Salmonella causes 1.3 million illnesses in the United States, with 19,000 hospitalizations and 380 deaths. Although there are several vaccines against S. typhi, they are only moderately efficient, are costly and multiple immunizations are necessary. There is no licensed vaccine against S. paratyphi A, B and C and Nontyphoidal Salmonella. Recombinant attenuated Salmonella vaccines (RASVs) can deliver antigens from a variety of pathogens, generating a range of immune responses including serum and mucosal antibodies, and a panoply of cell-mediated immune responses at local and distal sites. We hypothesize that RASVs with innovative features manipulate cell surface synthesizing protective antigens from Salmonella could induce protective immune responses to multiple Salmonella serovars. To test it, we propose new strategies using triple sugar regulation of cell surface components in vivo, and regulated production of Generalized Modules for Membrane Antigens in vivo to augment the immune responses against conserved surface antigens. The RASV strains with triple sugar regulation will be used to deliver conserved protective antigens from Salmonella to induce cross protection to multiple virulent Salmonella serovars.
To develop effective recombinant attenuated Salmonella vaccines (RASVs) against multiple virulent Salmonella serovars, we will explore innovated strategy using triple sugars to manipulate cell surface components in group B RASV-Typhimurium and group D RASV-Enteritidis in order to deliver conserved Salmonella antigens as vaccines against prevalent Salmonella serovars. This innovation can lead to one or more broader spectrum of Salmonella vaccines against multiple Salmonella serovars. These studies will also help to develop live attenuated Salmonella typhi and Salmonella paratyphi A vaccine candidates suitable for human use.
