Target Antigen Identification to Generate a Cross-serovar Salmonella Vaccine

Project Summary Systemic Salmonella infections are caused by distinct serovar groups that are typically defined as typhoidal, paratyphoid, or non-typhoidal. While there are new conjugate vaccines for typhoid, there are still no licensed vaccines for systemic Salmonellosis caused by paratyphoid or non-typhoidal serovars, despite the fact that these infections account for more than 50% of all deaths. Much of what we know about Salmonella protective immunity comes from researchers who study non-typhoidal strains in a mouse model since typhoid and paratyphoid strains do not infect any experimental animals. In this renewal application we describe the generation of a new mouse model that will allow side-by-side analysis of typhoidal and non-typhoidal disease. This is an important first step in understanding protective immunity to these different infections as a foundation for cross-serovar vaccine development. We will use this mouse model to, (i) compare host immunity and vaccine approaches to typhoidal and non-typhoidal Salmonella side-by-side in an animal model for the first time, (ii) identify new protective antigen targets of liver Tissue Resident Memory (TRM) CD4 T cells that protect against typhoidal, non-typhoidal, and Paratyphi infections. Together, these studies will provide the foundation for the development of a cross-serovar vaccine for all major causes of systemic Salmonellosis.