In spite of being perceived as a disease of the past, syphilis remains a serious global health problem, affecting
millions worldwide in both developing and developed countries. In underprivileged setting, syphilis is a significant
cause of stillbirth and neonatal mortality due to vertical transmission during pregnancy, while in developed
countries, it affects particularly high risk groups such as men who have sex with men (MSM). If untreated, syphilis
often results in serious neurological and cardiovascular complications, including blindness, deafness, stroke and
aortic aneurism. A better and simpler diagnostic test is desired to replace the current two-assay diagnostic tests,
especially if early diagnosis and disease staging can be distinguished. A practical proteome-scale platform for
antibody profiling has never before been available to the syphilis research community, and this technology has
the power to rapidly discovery novel biomarkers and improve syphilis diagnostics approaches. Antigen
Discovery, Inc. (ADI) of Irvine, CA, will develop a Treponema pallidum subspecies pallidum (TP) panproteome
microarray to measure specific anti-TP IgG and IgM antibody levels in longitudinally collected sera from rabbits
experimentally infected with syphilis agents and in patient sera. To this end, ADI will partner with two established
syphilis investigators, Dr. Lorenzo Giacani, based at the University of Washington and expert in the use of the
rabbit model of syphilis, and Dr. Jeffrey Klausner, based at UCLA, renowned for his syphilis epidemiological
studies in MSM and transgender women in Lima, Peru.The panproteome array will include up to 1,000 syphilis
proteins representing two groups of modern syphilis strains currently circulating globally. We hypothesize that
certain anti-TP antibodies can serve as biomarkers to detect early infections or repeat infections, as well as
different disease stages. The most promising diagnostic candidates will be identified in the rabbit model, which
has exquisite control over the timing of sample collection after infection, treatment and reinfection. Subsequently,
the top candidates will be confirmed in humans by testing the sera from Peruvian patients with varying stages of
disease. We expect to identify several TP proteins that are recognized by antibodies, some which appear soon
after infection and some that correlate with the stage of disease. Future studies will validate diagnostic markers
and develop a prototype diagnostic test that can be tested for FDA 510(k) clearance. This application addresses
the necessity of simplifying and improving syphilis diagnostics approaches, and choses to do it through the
application of an innovative proteomic technology mastered by ADI. If successful, our endeavor will provide new
tools and knowledge to help stem the spread of this serious infection.
