Current status of syphilis vaccine development: Need, challenges, prospects

Vaccine

Volumn 32, Issue 14, 2014, Pages 1602-1609

  Cameron, Caroline E ^a   Lukehart, Sheila A ^b  

^a UNIVERSITY OF VICTORIA   (Canada)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Animal model; Congenital infection; HIV susceptibility; Latent infection; Syphilis; Treponema pallidum; Vaccine development

Indexed keywords

BACTERIAL ANTIGEN; BACTERIAL VACCINE; SYPHILIS VACCINE; UNCLASSIFIED DRUG;

ADOPTIVE TRANSFER; ANTIBIOTIC THERAPY; ARTICLE; BACTERIAL TRANSMISSION; CELLULAR IMMUNITY; CONGENITAL SYPHILIS; DISEASE ELIMINATION; DISEASE MODEL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROMOTER REGION; PUBLIC HEALTH; SECONDARY SYPHILIS; SEXUAL TRANSMISSION; SEXUALLY TRANSMITTED DISEASE; SYPHILIS; TREPONEMA PALLIDUM; VACCINATION; VIRUS TRANSMISSION;

ANIMAL MODEL; CONGENITAL INFECTION; HIV SUSCEPTIBILITY; LATENT INFECTION; SYPHILIS; TREPONEMA PALLIDUM; VACCINE DEVELOPMENT;

ANIMALS; ANTITREPONEMAL AGENTS; BACTERIAL VACCINES; DISEASE MODELS, ANIMAL; HUMANS; PENICILLINS; SYPHILIS; SYPHILIS, CONGENITAL; TREPONEMA PALLIDUM; VACCINATION;

EID: 84896725484     PISSN: 0264410X     EISSN: 18732518     Source Type: Journal    
DOI: 10.1016/j.vaccine.2013.09.053     Document Type: Article

References (105)

1. World Health Organization Prevalence and incidence of selected sexually transmitted infections Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis and Trichomonas vaginalis: methods and results used by WHO to generate 2005 estimates 2011, World Health Organization, Geneva.
2. World Health Organization Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates. 2001 2013, World Health Organization, Geneva.
3. Herbert L.J., Middleton S.I. An estimate of syphilis incidence in Eastern Europe. J Glob Health 2012, 2(1):10402.
4. Savage E.J., Hughes G., Ison C., Lowndes C.M. Syphilis and gonorrhoea in men who have sex with men: a European overview. Euro Surveill 2009, 14(47):1-8.
5. Simms I., Fenton K.A., Ashton M., Turner K.M., Crawley-Boevey E.E., Gorton R., et al. The re-emergence of syphilis in the United Kingdom: the new epidemic phases. Sex Transm Dis 2005, 32(4):220-226.
6. Savage E.J., Marsh K., Duffell S., Ison C.A., Zaman A., Hughes G. Rapid increase in gonorrhoea and syphilis diagnoses in England in 2011. Euro Surveill 2012, 17(29).
7. Syphilis on the rise in the USA. Lancet 2011, 378(9791):542.
8. Centers for Disease Control and Prevention Sexually Transmitted Disease Surveillance 2009 2010, CDC.
9. Canadian sexually transmitted infections surveillance report. Can Commun Dis Rep 2007, 33(Suppl 1):1-69.
10. Botham S.J., Ressler K.A., Bourne C., Ferson M.J. Epidemic infectious syphilis in inner Sydney - strengthening enhanced surveillance. Aust N Z J Public Health 2006, 30(6):529-533.
11. Lee D.M., Chen M.Y. The re-emergence of syphilis among homosexually active men in Melbourne. Aust N Z J Public Health 2005, 29(4):390-391.
12. Azariah S. Is syphilis resurgent in New Zealand in the 21st century? A case series of infectious syphilis presenting to the Auckland Sexual Health Service. N Z Med J 2005, 118(1211):U1349.
13. Tucker J.D., Chen X.S., Peeling R.W. Syphilis and social upheaval in China. N Engl J Med 2010, 362(18):1658-1661.
14. Tucker J.D., Cohen M.S. China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses. Curr Opin Infect Dis 2011, 24(1):50-55.
15. Goldenberg R.L., Thompson C. The infectious origins of stillbirth. Am J Obstet Gynecol 2003, 189(3):861-873.
16. Watson-Jones D., Changalucha J., Gumodoka B., Weiss H., Rusizoka M., Ndeki L., et al. Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy. J Infect Dis 2002, 186(7):940-947.
17. Lozano R., Naghavi M., Foreman K., Lim S., Shibuya K., Aboyans V., et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380(9859):2095-2128.
18. Singh A.E., Sutherland K., Lee B., Robinson J.L., Wong T. Resurgence of early congenital syphilis in Alberta. CMAJ 2007, 177(1):33-36.
19. Hotez P.J. Neglected infections of poverty in the United States of America. PLoS Negl Trop Dis 2008, 2(6):e256.
20. Douglas J.M. Penicillin treatment of syphilis: clearing away the shadow on the land. JAMA 2009, 301(7):769-771.
21. White R.G., Orroth K.K., Korenromp E.L., Bakker R., Wambura M., Sewankambo N.K., et al. Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study. J Acquir Immune Defic Syndr 2004, 37(4):1500-1513.
22. Workowski K.A., Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010, 59(RR-12):1-110.
23. Ho E.L., Lukehart S.A. Syphilis: using modern approaches to understand an old disease. J Clin Invest 2011, 121(12):4584-4592.
24. Centers for Disease Control and Prevention, 2000, [accessed 05.03.13]. http://www.cdc.gov/stopsyphilis.
25. Centers for Disease Control and Prevention The national plan to eliminate syphilis from the United States 2006, U.S. Department of Health and Human Services, Atlanta, http://http://www.cdc.gov/stopsyphilis/seeplan2006.pdf. 2006 [accessed 05.03.13].
26. World Health Organization The global elimination of congenital syphilis: rationale and strategy for action 2007, http://www.who.int/reproductivehealth/publications/rtis/9789241595858/en/index.html [accessed 05.03.13].
27. Brown D.L., Frank J.E. Diagnosis and management of syphilis. Am Fam Physician 2003, 68(2):283-290.
28. Celum C.L. Sexually transmitted infections and HIV: epidemiology and interventions. Top HIV Med 2010, 18(4):138-142.
29. Mabey D., Peeling R.W., Ballard R., Benzaken A.S., Galbán E., Changalucha J., et al. Prospective, multi-centre clinic-based evaluation of four rapid diagnostic tests for syphilis. Sex Transm Infect 2006, 82(5):13-16.
30. Newman L., Kamb M., Hawkes S., Gomez G., Say L., Seuc A., et al. Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data. PLoS Med 2013, 10(2):e1001396.
31. Gray R.H., Wawer M.J., Sewankambo N.K., Serwadda D., Li C., Moulton L.H., et al. Relative risks and population attributable fraction of incident HIV associated with symptoms of sexually transmitted diseases and treatable symptomatic sexually transmitted diseases in Rakai District, Uganda. Rakai Project Team. AIDS 1999, 13(15):2113-2123.
32. Charon N.W., Goldstein S.F. Genetics of motility and chemotaxis of a fascinating group of bacteria: the spirochetes. Annu Rev Genet 2002, 36:47-73.
33. Fraser C.M., Norris S.J., Weinstock G.M., White O., Sutton G.G., Dodson R., et al. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 1998, 281(5375):375-388.
34. Cejkoá D., Zobaniká M., Chen L., Pospišilová P., Strouhal M., Qin X., et al. Whole genome sequences of three Treponema palidum ssp. pertenue strains: yaws and syphilis treponemes differ in less than 0.2% of the genome sequence. PLoS Negl Trop Dis 2012, 6(1):e1471.
35. Radolf J.D., Steiner B., Shevchenko D. Treponema pallidum: doing a remarkable job with what it's got. Trends Microbiol 1999, 7(1):7-9.
36. LaFond R.E., Lukehart S.A. Biological basis for syphilis. Clin Microbiol Rev 2006, 19(1):29-49.
37. Lukehart S.A., Hook E.W., Baker-Zander S.A., Collier A.C., Critchlow C.W., Handsfield H.H. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann Intern Med 1988, 109(11):855-862.
38. Raiziss G.W., Severac M. Rapidity with which Spirochaeta pallida invades the bloodstream. Arch Dermatol Syphilol 1937, 35:1101-1109.
39. Cumberland M.C., Turner T.B. Rate of multiplication of Treponema pallidum in normal and immune rabbits. Am J Syph 1949, 33:201-212.
40. Riviere G.R., Thomas D.D., Cobb C.M. In vitro model of Treponema pallidum invasiveness. Infect Immun 1989, 57(8):2267-2271.
41. Thomas D.D., Navab M., Haake D.A., Fogelman A.M., Miller J.N., Lovett M.A. Treponema pallidum invades intercellular junctions of endothelial cell monolayers. Proc Natl Acad Sci U S A 1988, 85(10):3608-3612.
42. Brinkman M.B., McGill M.A., Pettersson J., Rogers A., Matejková P., Smajs D., et al. A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin. Infect Immun 2008, 76(5):1848-1857.
43. Cameron C.E., Brown E.L., Kuroiwa J.M.Y., Schnapp L.M., Brouwer N.L. Treponema pallidum fibronectin-binding proteins. J Bacteriol 2004, 186:7019-7022.
44. Cameron C.E. Identification of a Treponema pallidum laminin-binding protein. Infect Immun 2003, 71(5):2525-2533.
45. Cameron C.E., Brouwer N.L., Tisch L.M., Kuroiwa J.M.Y. Defining the interaction of the Treponema pallidum adhesin Tp0751 with laminin. Infect Immun 2005, 73:7485-7494.
46. Cameron C.E., Kuroiwa J.M., Yamada M., Francescutti T., Chi B., Kuramitsu H.K. Heterologous expression of the Treponema pallidum laminin-binding adhesin Tp0751 in the culturable spirochete Treponema phagedenis. J Bacteriol 2008, 190(7):2565-2571.
47. Houston S., Hof R., Francescutti T., Hawkes A., Boulanger M.J., Cameron C.E. Bifunctional role of the Treponema pallidum extracellular matrix binding adhesin Tp0751. Infect Immun 2011, 79(3):1386-1398.
48. Houston S., Hof R., Honeyman L., Hassler J., Cameron C.E. Activation and proteolytic activity of the Treponema pallidum metalloprotease, pallilysin. PLoS Pathog 2012, 8(7):e1002822.
49. Lukehart S.A., Baker-Zander S.A., Lloyd R.M., Sell S. Characterization of lymphocyte responsiveness in early experimental syphilis. II. Nature of cellular infiltration and Treponema pallidum distribution in testicular lesions. J Immunol 1980, 124(1):461-467.
50. Van Voorhis W.C., Barrett L.K., Nasio J.M., Plummer F.A., Lukehart S.A. Lesions of primary and secondary syphilis contain activated cytolytic T cells. Infect Immun 1996, 64(3):1048-1050.
51. Salazar J.C., Cruz A.R., Pope C.D., Valderrama L., Trujillo R., Saravia N.G., Radolf J.D. Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis. J Infect Dis 2007, 195(6):879-887.
52. Stary G., Klein I., Brüggen M.C., Kohlhofer S., Brunner P.M., Spazierer D., et al. Host defense mechanisms in secondary syphilitic lesions: a role for IFN-gamma-/IL-17-producing CD8+ T cells?. Am J Pathol 2010, 177(5):2421-2432.
53. Baker-Zander S.A., Lukehart S.A. Macrophage-mediated killing of opsonized Treponema pallidum. J Infect Dis 1992, 165(1):69-74.
54. Lukehart S.A., Shaffer J.M., Baker-Zander S.A. A subpopulation of Treponema pallidum is resistant to phagocytosis: possible mechanism of persistence. J Infect Dis 1992, 166(6):1449-1453.
55. Medici M.A. The immunoprotective niche - a new pathogenic mechanism for syphilis, the systemic mycoses and other infectious diseases. J Theor Biol 1972, 36(3):617-625.
56. Walker E.M., Zampighi G.A., Blanco D.R., Miller J.N., Lovett M.A. Demonstration of rare protein in the outer membrane of Treponema pallidum subsp. pallidum by freeze-fracture analysis. J Bacteriol 1989, 171(9):5005-5011.
57. Radolf J.D., Norgard M.V., Schulz W.W. Outer membrane ultrastructure explains the limited antigenicity of virulent Treponema pallidum. Proc Natl Acad Sci U S A 1989, 86(6):2051-2055.
58. Liu J., Howell J.K., Bradley S.D., Zheng Y., Zhou Z.H., Norris S.J. Cellular architecture of Treponema pallidum: novel flagellum, periplasmic cone, and cell envelope as revealed by cryo electron tomography. J Mol Biol 2010, 403(4):546-561.
59. Izard J., Renken C., Hsieh C.E., Desrosiers D.C., Dunham-Ems S., La Vake C., et al. Cryo-electron tomography elucidates the molecular architecture of Treponema pallidum, the syphilis spirochete. J Bacteriol 2009, 191(24):7566-7580.
60. Radolf J.D. Treponema pallidum and the quest for outer membrane proteins. Mol Microbiol 1995, 16(6):1067-1073.
61. Centurion-Lara A., Castro C., Barrett L., Cameron C., Mostowfi M., Van Voorhis W.C., Lukehart S.A. Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response. J Exp Med 1999, 189:647-656.
62. Anand A., Luthra A., Dunham-Ems S., Caimano M.J., Karanian C., LeDoyt M., et al. TprC/D (Tp0117/131), a trimeric, pore-forming rare outer membrane protein of Treponema pallidum, has a bipartite domain structure. J Bacteriol 2012, 194(9):2321-2333.
63. Giacani L., Molini B.J., Kim E.Y., Godornes B.C., Leader B.T., Tantalo L.C., et al. Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis. J Immunol 2010, 184(7):3822-3829.
64. Giacani L., Lukehart S., Centurion-Lara A. Length of guanosine homopolymeric repeats modulates promoter activity of subfamily II tpr genes of Treponema pallidum ssp. pallidum. FEMS Immunol Med Microbiol 2007, 51(2):289-301.
65. Centurion-Lara A., Godornes C., Castro C., Van Voorhis W.C., Lukehart S.A. The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles. Infect Immun 2000, 68(2):824-831.
66. Centurion-Lara A., LaFond R.E., Hevner K., Godornes C., Molini B.J., Van Voorhis W.C., Lukehart S.A. Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection. Mol Microbiol 2004, 52:1579-1596.
67. LaFond R.E., Molini B.J., Van Voorhis W.C., Lukehart S.A. Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis. Infect Immun 2006, 74(11):6244-6251.
68. Centurion-Lara A., Giacani L., Godornes C., Molini B.J., Brinck R.T., Lukehart S.A. Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains. PLoS Negl Trop Dis 2013, 7(5):e2222.
69. Cox D.L., Luthra A., Dunham-Ems S., et al. Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum. Infect Immun 2010, 78(12):5178-5194.
70. Desrosiers D.C., Anand A., Luthra A., Dunham-Ems S., LeDoyt M., Cummings M.A., et al. TP0326, a Treponema pallidum beta-barrel assembly machinery A (BamA) orthologue and rare outer membrane protein. Mol Microbiol 2011, 80(6):1496-1515.
71. Cameron C.E., Lukehart S.A., Castro C., Molini B., Godornes C., Van Voorhis W.C. Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92. J Infect Dis 2000, 181(4):1401-1413.
72. Sun E.S., Molini B.J., Barrett L.K., Centurion-Lara A., Lukehart S.A., Subfamily Van Voorhis W.C. I Treponema pallidum repeat protein family: sequence variation and immunity. Microbes Infect 2004, 6(8):725-737.
73. Tantalo L.C., Lukehart S.A., Marra C.M. Treponema pallidum strain-specific differences in neuroinvasion and clinical phenotype in a rabbit model. J Infect Dis 2005, 191(1):75-80.
74. Fitzgerald T.J. Experimental congenital syphilis in rabbits. Can J Microbiol 1985, 31(9):757-762.
75. Godornes C., Leader B.T., Molini B.J., Centurion-Lara A., Lukehart S.A. Quantitation of rabbit cytokine mRNA by real-time RT-PCR. Cytokine 2007, 38(1):1-7.
76. Miller J.N. Immunity in experimental syphilis. VI. Successful vaccination of rabbits with Treponema pallidum, Nichols strain, attenuated by γ-irradiation. J Immunol 1973, 110(5):1206-1215.
77. Magnuson H.J., Halbert S.P., Rosenau B.J. Attempted immunization of rabbits against syphilis with killed Treponema pallidum and adjuvants. J Vener Dis Inf 1947, 28:267-271.
78. Eagle H., Fleischman R. The antibody response in rabbits to killed suspensions of pathogenic Treponema pallidum. J Exp Med 1948, 87:369-384.
79. Waring G.W., Fleming W.L. Further attempts to immunize rabbits with killed Treponema pallidum. Am J Syph Gonorrhea Vener Dis 1951, 35:568-572.
80. McLeod C.P., Magnuson H.J. Production of immobilizing antibodies unaccompanied by active immunity to Treponema pallidum as shown by injecting rabbits and mice with the killed organisms. Am J Syph Gonorrhea Vener Dis 1953, 37(1):9-22.
81. McLeod C.P. Antigenicity in rabbits and relation to immunity. Public Health Rep 1962, 77(5):431-436.
82. Izzat N.N., Knox J.M., Dacres W.G., Smith E.B. Resistance and serological changes in rabbits immunized with virulent Treponema pallidum sonicate. Acta Derm Venereol 1971, 51(2):157-160.
83. Lukehart S.A. Prospects for development of a treponemal vaccine. Rev Infect Dis 1985, 7(2):S305-S313.
84. Cullen P.A., Cameron C.E. Progress towards an effective syphilis vaccine: the past, present and future. Expert Rev Vaccines 2006, 5(1):67-80.
85. Baker-Zander S.A., Shaffer J.M., Lukehart S.A. VDRL antibodies enhance phagocytosis of Treponema pallidum by macrophages. J Infect Dis 1993, 167(5):1100-1105.
86. Blanco D.R., Champion C.I., Dooley A., Cox D.L., Whitelegge J.P., Faull K., Lovett M.A. A monoclonal antibody that conveys in vitro killing and partial protection in experimental syphilis binds a phosphorylcholine surface epitope of Treponema pallidum. Infect Immun 2005, 73(5):3083-3095.
87. Chesney A.M., Kemp J.E. On variations in the response of treated rabbits to reinoculation; and on cryptogenic reinfection with syphilis. J Exp Med 1926, 44:589-606.
88. Magnuson H.J., Rosenau B.J. The rate of development and degree of acquired immunity in experimental syphilis. Am J Syph Gonorrhea Vener Dis 1948, 32(5):418-436.
89. Magnuson H.J., Rosenau B.J., Clark J.W. The duration of acquired immunity in experimental syphilis. Am J Syph Gonorrhea Vener Dis 1949, 33(4):297-302.
90. Turner T.B., Nelson R.A. The relationship of treponemal immobilizing antibody to immunity in syphilis. Trans Assoc Am Physicians 1950, 63:112-117.
91. Bishop N.H., Miller J.N. Humoral immunity in experimental syphilis. I. The demonstration of resistance conferred by passive immunization. J Immunol 1976, 117(1):191-196.
92. Schell R.F., Chan J.K., Le Frock J.L. Endemic syphilis: passive transfer of resistance with serum and cells in hamsters. J Infect Dis 1979, 140(3):378-383.
93. Morgan C.A., Lukehart S.A., Van Voorhis W.C. Immunization with the N-terminal portion of Treponema pallidum repeat protein K attenuates syphilitic lesion development in the rabbit model. Infect Immun 2002, 70(12):6811-6816.
94. Cameron C.E., Castro C., Lukehart S.A., Van Voorhis W.C. Function and protective capacity of Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase. Infect Immun 1998, 66(12):5763-5770.
95. Magnuson H.J., Thomas E.W., Olansky S., Kaplan B.I., DeMello L., Cutler J.C. Inoculation syphilis in human volunteers. Medicine 1956, 35(1):33-82.
96. Turner T.B., Hollander D.H. Biology of the Treponematoses 1957, World Health Organization, Geneva.
97. Andre F.E. How the research-based industry approaches vaccine development and establishes priorities. Dev Biol (Basel) 2002, 110:25-29.
98. Bill Melinda Gates Foundation Global health leaders launch Decade of Vaccines collaboration. 2010 Feb 12.
99. Carney S. How can we avoid the productivity gap?. Drug Discov Today 2005, 10(15):1011-1013.
100. Keith J.A., Agostini B.L., Arthur P.A., Maes E., Daems R. Delivering the promise of the decade of vaccines: opportunities and challenges in the development of high quality new vaccines. Vaccine 2013, 31(Suppl. 2):B184-B193.
101. Salazar J.C., Hazlett K.R., Radolf J.D. The immune response to infection with Treponema pallidum, the stealth pathogen. Microbes Infect 2002, 4(11):1133-1140.
102. Bloom D.E. The value of vaccination. Adv Exp Med Biol 2011, 697:1-8.
103. Giacani L., Sambri V., Marangoni A., Cavrini F., Storni E., Donati M., et al. Immunological evaluation and cellular location analysis of the TprI antigen of Treponema pallidum subsp. pallidum. Infect Immun 2005, 73(6):3817-3822.
104. Houston S., Cameron C.E. Treponema pallidum dissemination; facilitating immune evasion and bacterial persistence. The Pathogenic Spirochetes: Strategies for Evasion of Host Immunity and Persistence 2012, Springer Science and Business Media, New York, NY. M. Embers (Ed.).
105. Brautigam C.A., Deka R.K., Ouyang Z., Machius M., Knutsen G., Tomchick D.R., Norgard M.V. Biophysical and bioinformatic analyses implicate the Treponema pallidum Tp34 lipoprotein (Tp0971) in transition metal homeostasis. J Bacteriol 2012, 194(24):6771-6781.