Urinary tract infections (UTIs) cause approximately 400 million infections per year and are responsible for nearly 30% of sepsis cases, causing > 200K deaths annually. Recurrent UTI causes prolonged negative impacts on quality of life, increased risk of severe complications and has no effective treatment. Current UTI vaccines under development demonstrate variable efficacy in human trials despite promising pre-clinical data. Hindering progression of UTI vaccines is a lack of correlates of protection and understanding of the optimal immune response required to prevent UTI recurrence. Evidence from mice lacking mature lymphocytes suggests a key role for adaptive immune responses in Uropathogenic Escherichia coli (UPEC) clearance, but the exact mechanism or immune cells required for protection against UTI or sepsis remains undefined. We are investigating the B and T cell responses induced by candidate vaccines to identify new correlates of protection against UTI and sepsis. Establishing correlates of protection for UTI and urosepsis would dramatically advance vaccine and related therapeutic development.