Background Syphilis is resurgent in many developed countries, including the United States, and still prevalent in developing nations, where it causes significant morbidity in adults and mortality when infection is congenital. Such evidence highlights the need for novel control strategies to curtail syphilis spread, including the development of a vaccine. Although some of the most promising vaccine candidates have been identified among the putative surface-exposed integral outer membrane antigens of the syphilis spirochete, immunization/challenge experiments using denatured/refolded recombinants did not fully protect animals against infection in the rabbit model of syphilis. We speculated that immunizing with antigens in their native structure and with a delivery approach that simulates the antigen cellular compartment could increase the protective ability of these vaccine candidates.

Methods To test our hypothesis, we engineered a lab-derived non-pathogenic Borrelia burgdorferi strain to express the tp0897 and tp0435 genes of Treponema pallidum subsp. pallidum and immunized rabbits by injecting recombinant strain intramuscularly without adjuvant. The tp0897 and tp0435 genes encode the putative integral outer membrane protein TprK, and the abundantly expressed periplasmic/surface 17-kDa lipoprotein (Tp0435) of the syphilis agent, respectively. Following the development of a specific response to these treponemal antigens in immunized animals, rabbits were challenged with the Nichols strain of Treponema pallidum. Primary lesion development and treponemal burden within lesions were measured using dark-field microscopy and real time RT-qPCR, while serology was used to assess establishment of the infection.

Results No protection was seen in rabbits immunized with Borrelia expressing Tp0435 and only partial protection in animals immunized with Borrelia expressing TprK.

Conclusion Our surrogate Borrelia system is an effective delivery system to elicit a specific response to Treponema pallidum antigens. This novel approach will help assess the efficacy of syphilis vaccine candidates

Disclosure No significant relationships.