Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum subspecies pallidum (T. pallidum). Syphilis is still a global health concern, as its incidence is rising in high-income countries like the United States and it is still endemic in low-income countries, where it causes significant mortality due to congenital transmission. Our chances at syphilis control would improve if a vaccine against syphilis was available. The past century of research has only yielded experimental vaccines able to produce partial protection, but the use of new techniques could improve this outcome. One possibility would be to use an array of known protective epitopes from other T. pallidum antigens crafted onto a protein carrier to induce a protective immune response. Currently, we are investigating the use of the Tp17 protein of T. pallidum as a scaffolding for a future vaccine. The Tp17 protein has a β-barrel structure with loops around the edges of the barrel. To use this protein as a scaffolding for a vaccine, we will be performing epitope mapping to determine the hierarchy of immunodominant epitopes in Tp17 to find the ideal candidate regions that will be substituted with other epitopes. We are using Enzyme-Linked Immunosorbent Assay (ELISA) to attain these data in combination with human sera to define the reactivity of the different peptides. The results will determine the most immunogenic peptides, thus indicating the ideal areas to be replaced by protective epitopes in a potential vaccine. We anticipate that several of the most reactive peptides will correspond to the protein loops outside of the β-barrel, which should be easily replaceable without affecting Tp17 structure.

Syphilis is a sexually transmitted infection (STI) that is caused by the bacterium Treponema pallidum. STIs within the U.S. remain at a concerning all-time high, with syphilis incidence increasing by 52% since 2016. Syphilis remains endemic in many low- and middle-income regions such as sub-Saharan Africa. A vaccine that’s able to provide complete protection would be an important solution in controlling this infection. To date, there has been a single study producing complete protection that was conducted by immunizing rabbits a total of 60 times, which is impractical in humans patients, but proves that protection can be achieved through immunization. Partial protection has been achieved using recombinant proteins, a method that in our laboratory allowed the identification of possible protective epitopes on T. pallidum specific antigens. Though a vaccine design able to elicit complete protection remains elusive, a chimeric mRNA-based vaccine could breathe new life into the search. This project’s main purpose is to map the immunogenic epitopes of the Tp17 lipoprotein of the syphilis pathogen with the goal of using it as a scaffolding protein for a chimeric vaccine. To this end, we have broken down the Tp17 protein into 23 20-mer peptides overlapping by 10 amino acids and used infected rabbit sera to test and identify the regions of the protein that elicit the most robust humoral response using enzyme-linked immunosorbent assays (ELISA). Preliminary data has shown that the hypothesized external loops in the structure of Tp17 are the regions of highest immunoreactivity. These reactive epitopes were mapped onto the determined Tp17 structure to create a hierarchy of regions that could be replaced with B-cell epitopes protective against syphilis that our lab has previously identified with the future goal to create and test a chimeric mRNA vaccine.