TARGET ANTIGEN IDENTIFICATION TO IMPROVE SALMONELLA VACCINATION

Typhoid and Non-Typhoidal Salmonellosis (NTS) are systemic diseases that annually cause 1 million globaldeaths. Given the impact of these infections on infants, the elderly, and immune suppressed individudals, asafe and effective sub-unit vaccine could have an enormous impact on this disease. While significant gainshave been made in identifying the Salmonella target antigens recognized by systemic immune responses, westill know almost nothing about the target antigens recognized by tissue resident lymphocytes, a populationthat we now know is critical for the protective efficacy of live Salmonella vaccines. This application will focus onprotective tissue resident memory (TRM) Th1 cells elicited by a protective live Salmonella vaccine and identifyprotective target antigens recognized by these cells. Our experimental approach is unique in that it will usenatural water contamination challenge, a mouse model where CD4 TRM Th1 cells actively participate inprotective immunity, and a set of tools that allow direct visualization of Salmonella-specific CD4 T cells. Ourapplication specifically proposes to, (i) determine the role of tissue-resident memory T cells in the elimination ofpersistent Salmonella, (ii) uncover the unique TRM T cell receptors that allow greater protection againstSalmonella infection, and (iii) identify the antigens recognized by this T cell subset and determine whether theycan improve the effectiveness of a sub-unit vaccine for Salmonella.