Progress towards an effective syphilis vaccine: the past, present and future.
Syphilis is a disease caused by infection with the spirochetal pathogen Treponema pallidum subspp. pallidum. Despite intensive efforts, the unusual biology of T. pallidum has hindered progress towards the development of a vaccine to prevent infection. This review describes previous endeavors to develop a syphilis vaccine, outlines the key issues in the field and proposes new directions in the design of a T. pallidum vaccine. Following a brief overview of the disease symptoms, epidemiology, diagnosis and treatment, a case is put forward for the benefit of pursuing a syphilis vaccine. Relevant material concerning immunity to T. pallidum infection is summarized and evaluated, and pilot experiments describing the use of whole-cell bacterin vaccines and similar preparations are included. A detailed section concerning subunit vaccines is provided, incorporating discussions pertaining to relevant antigen selection, the identification of putative T. pallidum surface-exposed outer membrane proteins, factors hindering previous attempts to vaccinate with recombinant outer membrane proteins, problems and pitfalls of syphilis outer membrane protein-based vaccines, anti-attachment vaccines and the potential use of nonprotein subunit preparations as vaccinogens. Subsequently, critical aspects concerning vaccine antigen preparation and delivery are noted, including protein conformation, synergy, post-translational modifications, live attenuated organisms as vaccine vectors, prime-boost methodologies, adjuvant selection and immunization routes. Finally, animal models are discussed with particular reference to immunoprotection studies. A more thorough understanding of immunity to syphilis, a comprehensive assessment of the immunoprotective capacity of the putative surface-accessible antigens of T. pallidum and utilization of the latest advances in vaccine science should set the scene for future development of a syphilis vaccine.
Cullen
Paul A
PA
Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, VIC 3800, Australia. pcullen@u.washington.edu
Cameron
Caroline E
CE
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005544:Forecasting; D006801:Humans; D007113:Immunity, Innate; D013587:Syphilis / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends*; D014210:Treponema pallidum / Q000276:immunology*
D001428:Bacterial Vaccines