Project 3: Specific T and B cell responses to candidate Treponema pallidum outer membrane protein vaccine antigens

Summary

The third Scientific Project investigates the premise that a detailed understanding of the acquired immune response to the T. pallidum vaccine candidate antigens (TpVCA) from Scientific Projects 1 and 2 will assist a reiterative process that will improve syphilis vaccine design.

State-of-the-art single B cell technology is used to isolate naïve and memory rabbit and human B cells that produce TpVCA-specific monoclonal antibodies (mAb), which are then functionally investigated in Scientific Projects 1 and 2 for a role in protection from infection. The epitopes recognized by the most potent mAbs are determined, as are the crystal structures of mAb-TpVCA complexes, to uncover the TpVCA domains that bear functional anti-bacterial epitopes. The TpVCA are assessed for prevalence and levels of CD4 TFH and TH1 cells in the blood of persons with symptomatic and asymptomatic T. pallidum infection, and the fate of T. pallidum-specific CD4 T-cells are classified as either migrating to the sites of infection or being retained as tissue resident memory T cells.  Prioritized vaccinogen formulations determined in Scientific Projects 1 and 2 are assessed in combination with custom human-track adjuvants in mouse humoral and CD4 immunogenicity assays.

Scientific Project 3 critically synergizes with the other Projects and Cores to downselect and optimize antigen formulations and adjuvants with the goal of delivering a lead T. pallidum vaccine candidate suitable for advancement to first-in-human clinical trials.