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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Mar 29;91(7):2456–2463. doi: 10.1073/pnas.91.7.2456

Vaccines for bacterial sexually transmitted infections: a realistic goal?

P F Sparling 1, C Elkins 1, P B Wyrick 1, M S Cohen 1
PMCID: PMC43388  PMID: 8146139

Abstract

Bacterial infections of the genital tract (gonorrhea, chlamydia, chancroid, syphilis) are common and cause significant morbidity. Their importance is heightened by recent appreciation of their roles in facilitation of transmission of the human immunodeficiency virus (HIV). Each is capable of causing repeated infections, suggesting lack of permanent broadly effective immunity. An effective vaccine has yet to be developed for any of these diseases. Rapid progress in understanding the molecular basis for pathogenesis of infection, including mechanisms for escape from otherwise effective immune surveillance and mechanisms for causing injury to host cells, has stimulated renewed efforts to make vaccines for some of these infections. Progress has been greatest for Neisseria gonorrhoeae and Chlamydia trachomatis. Present emphasis is on the major or principal outer membrane proteins of N. gonorrhoeae and C. trachomatis, based on evidence for neutralizing antibodies directed against surface-exposed variable domains of each of these proteins. Other surface-exposed proteins, including the iron-repressible transferrin receptor in gonococci and certain heat-shock proteins in chlamydia, also may be targets for vaccines. Although much remains to be learned, cautious optimism is warranted.

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Selected References

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  1. Abeck D., Johnson A. P. Pathophysiological concept of Haemophilus ducreyi infection (chancroid) Int J STD AIDS. 1992 Sep-Oct;3(5):319–323. doi: 10.1177/095646249200300503. [DOI] [PubMed] [Google Scholar]
  2. Abeck D., Korting H. C., Zaba R., Dangor Y., Fehler G., Ballard R. C. Soluble interleukin-2 receptors in serum and urine of patients with chancroid and their response to therapy. Int J STD AIDS. 1990 Jul;1(4):282–284. doi: 10.1177/095646249000100411. [DOI] [PubMed] [Google Scholar]
  3. Ala'Aldeen D. A., Powell N. B., Wall R. A., Borriello S. P. Localization of the meningococcal receptors for human transferrin. Infect Immun. 1993 Feb;61(2):751–759. doi: 10.1128/iai.61.2.751-759.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Allen J. E., Locksley R. M., Stephens R. S. A single peptide from the major outer membrane protein of Chlamydia trachomatis elicits T cell help for the production of antibodies to protective determinants. J Immunol. 1991 Jul 15;147(2):674–679. [PubMed] [Google Scholar]
  5. Allen J. E., Stephens R. S. An intermolecular mechanism of T cell help for the production of antibodies to the bacterial pathogen, Chlamydia trachomatis. Eur J Immunol. 1993 May;23(5):1169–1172. doi: 10.1002/eji.1830230529. [DOI] [PubMed] [Google Scholar]
  6. Apicella M. A., Shero M., Jarvis G. A., Griffiss J. M., Mandrell R. E., Schneider H. Phenotypic variation in epitope expression of the Neisseria gonorrhoeae lipooligosaccharide. Infect Immun. 1987 Aug;55(8):1755–1761. doi: 10.1128/iai.55.8.1755-1761.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Arko R. J. Animal models for pathogenic Neisseria species. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S56–S59. doi: 10.1128/cmr.2.suppl.s56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Arko R. J., Duncan W. P., Brown W. J., Peacock W. L., Tomizawa T. Immunity in infection with Neisseria gonorrhoeae: duration and serological response in the chimpanzee. J Infect Dis. 1976 Apr;133(4):441–447. [PubMed] [Google Scholar]
  9. Baehr W., Zhang Y. X., Joseph T., Su H., Nano F. E., Everett K. D., Caldwell H. D. Mapping antigenic domains expressed by Chlamydia trachomatis major outer membrane protein genes. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4000–4004. doi: 10.1073/pnas.85.11.4000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Baker-Zander S. A., Shaffer J. M., Lukehart S. A. VDRL antibodies enhance phagocytosis of Treponema pallidum by macrophages. J Infect Dis. 1993 May;167(5):1100–1105. doi: 10.1093/infdis/167.5.1100. [DOI] [PubMed] [Google Scholar]
  11. Beatty W. L., Byrne G. I., Morrison R. P. Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3998–4002. doi: 10.1073/pnas.90.9.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bhat K. S., Gibbs C. P., Barrera O., Morrison S. G., Jähnig F., Stern A., Kupsch E. M., Meyer T. F., Swanson J. The opacity proteins of Neisseria gonorrhoeae strain MS11 are encoded by a family of 11 complete genes. Mol Microbiol. 1991 Aug;5(8):1889–1901. doi: 10.1111/j.1365-2958.1991.tb00813.x. [DOI] [PubMed] [Google Scholar]
  13. Bishop N. H., Miller J. N. Humoral immunity in experimental syphilis. II. The relationship of neutralizing factors in immune serum to acquired resistance. J Immunol. 1976 Jul;117(1):197–207. [PubMed] [Google Scholar]
  14. Blanco D. R., Giladi M., Champion C. I., Haake D. A., Chikami G. K., Miller J. N., Lovett M. A. Identification of Treponema pallidum subspecies pallidum genes encoding signal peptides and membrane-spanning sequences using a novel alkaline phosphatase expression vector. Mol Microbiol. 1991 Oct;5(10):2405–2415. doi: 10.1111/j.1365-2958.1991.tb02086.x. [DOI] [PubMed] [Google Scholar]
  15. Blanton K. J., Biswas G. D., Tsai J., Adams J., Dyer D. W., Davis S. M., Koch G. G., Sen P. K., Sparling P. F. Genetic evidence that Neisseria gonorrhoeae produces specific receptors for transferrin and lactoferrin. J Bacteriol. 1990 Sep;172(9):5225–5235. doi: 10.1128/jb.172.9.5225-5235.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Borenstein L. A., Radolf J. D., Fehniger T. E., Blanco D. R., Miller J. N., Lovett M. A. Immunization of rabbits with recombinant Treponema pallidum surface antigen 4D alters the course of experimental syphilis. J Immunol. 1988 Apr 1;140(7):2415–2421. [PubMed] [Google Scholar]
  17. Boslego J. W., Tramont E. C., Chung R. C., McChesney D. G., Ciak J., Sadoff J. C., Piziak M. V., Brown J. D., Brinton C. C., Jr, Wood S. W. Efficacy trial of a parenteral gonococcal pilus vaccine in men. Vaccine. 1991 Mar;9(3):154–162. doi: 10.1016/0264-410x(91)90147-x. [DOI] [PubMed] [Google Scholar]
  18. Brunham R. C., Kuo C. C., Cles L., Holmes K. K. Correlation of host immune response with quantitative recovery of Chlamydia trachomatis from the human endocervix. Infect Immun. 1983 Mar;39(3):1491–1494. doi: 10.1128/iai.39.3.1491-1494.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Brunham R. C., Peeling R., Maclean I., McDowell J., Persson K., Osser S. Postabortal Chlamydia trachomatis salpingitis: correlating risk with antigen-specific serological responses and with neutralization. J Infect Dis. 1987 Apr;155(4):749–755. doi: 10.1093/infdis/155.4.749. [DOI] [PubMed] [Google Scholar]
  20. Butt N. J., Virji M., Vayreda F., Lambden P. R., Heckels J. E. Gonococcal outer-membrane protein PIB: comparative sequence analysis and localization of epitopes which are recognized by type-specific and cross-reacting monoclonal antibodies. J Gen Microbiol. 1990 Nov;136(11):2165–2172. doi: 10.1099/00221287-136-11-2165. [DOI] [PubMed] [Google Scholar]
  21. Byrne G. I., Lehmann L. K., Landry G. J. Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect Immun. 1986 Aug;53(2):347–351. doi: 10.1128/iai.53.2.347-351.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. COLLART P., BOREL L. J., DUREL P. SIGNIFICANCE OF SPIRAL ORGANISMS FOUND, AFTER TREATMENT, IN LATE HUMAN AND EXPERIMENTAL SYPHILIS. Br J Vener Dis. 1964 Jun;40:81–89. doi: 10.1136/sti.40.2.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Caldwell H. D., Perry L. J. Neutralization of Chlamydia trachomatis infectivity with antibodies to the major outer membrane protein. Infect Immun. 1982 Nov;38(2):745–754. doi: 10.1128/iai.38.2.745-754.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Cameron D. W., Simonsen J. N., D'Costa L. J., Ronald A. R., Maitha G. M., Gakinya M. N., Cheang M., Ndinya-Achola J. O., Piot P., Brunham R. C. Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet. 1989 Aug 19;2(8660):403–407. doi: 10.1016/s0140-6736(89)90589-8. [DOI] [PubMed] [Google Scholar]
  25. Carbonetti N. H., Simnad V. I., Seifert H. S., So M., Sparling P. F. Genetics of protein I of Neisseria gonorrhoeae: construction of hybrid porins. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6841–6845. doi: 10.1073/pnas.85.18.6841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Champion C. I., Miller J. N., Borenstein L. A., Lovett M. A., Blanco D. R. Immunization with Treponema pallidum endoflagella alters the course of experimental rabbit syphilis. Infect Immun. 1990 Sep;58(9):3158–3161. doi: 10.1128/iai.58.9.3158-3161.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Cheng X., Pal S., de la Maza L. M., Peterson E. M. Characterization of the humoral response induced by a peptide corresponding to variable domain IV of the major outer membrane protein of Chlamydia trachomatis serovar E. Infect Immun. 1992 Aug;60(8):3428–3432. doi: 10.1128/iai.60.8.3428-3432.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Clemetson D. B., Moss G. B., Willerford D. M., Hensel M., Emonyi W., Holmes K. K., Plummer F., Ndinya-Achola J., Roberts P. L., Hillier S. Detection of HIV DNA in cervical and vaginal secretions. Prevalence and correlates among women in Nairobi, Kenya. JAMA. 1993 Jun 9;269(22):2860–2864. [PubMed] [Google Scholar]
  29. Cohen M. S., Cannon J. G., Jerse A. E., Charniga L. M., Isbey S. F., Whicker L. G. Human experimentation with Neisseria gonorrhoeae: rationale, methods, and implications for the biology of infection and vaccine development. J Infect Dis. 1994 Mar;169(3):532–537. doi: 10.1093/infdis/169.3.532. [DOI] [PubMed] [Google Scholar]
  30. Connell T. D., Shaffer D., Cannon J. G. Characterization of the repertoire of hypervariable regions in the Protein II (opa) gene family of Neisseria gonorrhoeae. Mol Microbiol. 1990 Mar;4(3):439–449. doi: 10.1111/j.1365-2958.1990.tb00610.x. [DOI] [PubMed] [Google Scholar]
  31. Cornelissen C. N., Biswas G. D., Tsai J., Paruchuri D. K., Thompson S. A., Sparling P. F. Gonococcal transferrin-binding protein 1 is required for transferrin utilization and is homologous to TonB-dependent outer membrane receptors. J Bacteriol. 1992 Sep;174(18):5788–5797. doi: 10.1128/jb.174.18.5788-5797.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Danielsson D. Gonorrhoea and syphilis in Sweden--past and present. Scand J Infect Dis Suppl. 1990;69:69–76. [PubMed] [Google Scholar]
  33. Danilition S. L., Maclean I. W., Peeling R., Winston S., Brunham R. C. The 75-kilodalton protein of Chlamydia trachomatis: a member of the heat shock protein 70 family? Infect Immun. 1990 Jan;58(1):189–196. doi: 10.1128/iai.58.1.189-196.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. DePamphilis M. L. Origins of DNA replication in metazoan chromosomes. J Biol Chem. 1993 Jan 5;268(1):1–4. [PubMed] [Google Scholar]
  35. Dean D., Patton M., Stephens R. S. Direct sequence evaluation of the major outer membrane protein gene variant regions of Chlamydia trachomatis subtypes D', I', and L2'. Infect Immun. 1991 Apr;59(4):1579–1582. doi: 10.1128/iai.59.4.1579-1582.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Dean D., Schachter J., Dawson C. R., Stephens R. S. Comparison of the major outer membrane protein variant sequence regions of B/Ba isolates: a molecular epidemiologic approach to Chlamydia trachomatis infections. J Infect Dis. 1992 Aug;166(2):383–392. doi: 10.1093/infdis/166.2.383. [DOI] [PubMed] [Google Scholar]
  37. Elkins C., Carbonetti N. H., Coímbre A. J., Thomas C. E., Sparling P. F. Cloning and constitutive expression of structural genes encoding gonococcal porin protein in Escherichia coli and attenuated Salmonella typhimurium vaccine strains. Gene. 1994 Jan 28;138(1-2):43–50. doi: 10.1016/0378-1119(94)90781-1. [DOI] [PubMed] [Google Scholar]
  38. Elkins C., Carbonetti N. H., Varela V. A., Stirewalt D., Klapper D. G., Sparling P. F. Antibodies to N-terminal peptides of gonococcal porin are bactericidal when gonococcal lipopolysaccharide is not sialylated. Mol Microbiol. 1992 Sep;6(18):2617–2628. doi: 10.1111/j.1365-2958.1992.tb01439.x. [DOI] [PubMed] [Google Scholar]
  39. Elkins C., Rest R. F. Monoclonal antibodies to outer membrane protein PII block interactions of Neisseria gonorrhoeae with human neutrophils. Infect Immun. 1990 Apr;58(4):1078–1084. doi: 10.1128/iai.58.4.1078-1084.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Fehniger T. E., Radolf J. D., Lovett M. A. Properties of an ordered ring structure formed by recombinant Treponema pallidum surface antigen 4D. J Bacteriol. 1986 Mar;165(3):732–739. doi: 10.1128/jb.165.3.732-739.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Fitzgerald T. J. Syphilis vaccine: up-regulation of immunogenicity by cyclophosphamide, Ribi adjuvant, and indomethacin confers significant protection against challenge infection in rabbits. Vaccine. 1991 Apr;9(4):266–272. doi: 10.1016/0264-410x(91)90110-r. [DOI] [PubMed] [Google Scholar]
  42. Gotschlich E. C., Seiff M. E., Blake M. S., Koomey M. Porin protein of Neisseria gonorrhoeae: cloning and gene structure. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8135–8139. doi: 10.1073/pnas.84.22.8135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Gotschlich E. C., Seiff M., Blake M. S. The DNA sequence of the structural gene of gonococcal protein III and the flanking region containing a repetitive sequence. Homology of protein III with enterobacterial OmpA proteins. J Exp Med. 1987 Feb 1;165(2):471–482. doi: 10.1084/jem.165.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Haas R., Meyer T. F. Molecular principles of antigenic variation in Neisseria gonorrhoeae. Antonie Van Leeuwenhoek. 1987;53(6):431–434. doi: 10.1007/BF00415498. [DOI] [PubMed] [Google Scholar]
  45. Hagblom P., Segal E., Billyard E., So M. Intragenic recombination leads to pilus antigenic variation in Neisseria gonorrhoeae. Nature. 1985 May 9;315(6015):156–158. doi: 10.1038/315156a0. [DOI] [PubMed] [Google Scholar]
  46. Haines K. A., Yeh L., Blake M. S., Cristello P., Korchak H., Weissmann G. Protein I, a translocatable ion channel from Neisseria gonorrhoeae, selectively inhibits exocytosis from human neutrophils without inhibiting O2- generation. J Biol Chem. 1988 Jan 15;263(2):945–951. [PubMed] [Google Scholar]
  47. Igietseme J. U., Rank R. G. Susceptibility to reinfection after a primary chlamydial genital infection is associated with a decrease of antigen-specific T cells in the genital tract. Infect Immun. 1991 Apr;59(4):1346–1351. doi: 10.1128/iai.59.4.1346-1351.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. KELLOGG D. S., Jr, PEACOCK W. L., Jr, DEACON W. E., BROWN L., PIRKLE D. I. NEISSERIA GONORRHOEAE. I. VIRULENCE GENETICALLY LINKED TO CLONAL VARIATION. J Bacteriol. 1963 Jun;85:1274–1279. doi: 10.1128/jb.85.6.1274-1279.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Kiviat N. B., Paavonen J. A., Wølner-Hanssen P., Critchlow C. W., Stamm W. E., Douglas J., Eschenbach D. A., Corey L. A., Holmes K. K. Histopathology of endocervical infection caused by Chlamydia trachomatis, herpes simplex virus, Trichomonas vaginalis, and Neisseria gonorrhoeae. Hum Pathol. 1990 Aug;21(8):831–837. doi: 10.1016/0046-8177(90)90052-7. [DOI] [PubMed] [Google Scholar]
  50. Knapp J. S., Tam M. R., Nowinski R. C., Holmes K. K., Sandström E. G. Serological classification of Neisseria gonorrhoeae with use of monoclonal antibodies to gonococcal outer membrane protein I. J Infect Dis. 1984 Jul;150(1):44–48. doi: 10.1093/infdis/150.1.44. [DOI] [PubMed] [Google Scholar]
  51. Koehler J. E., Birkelund S., Stephens R. S. Overexpression and surface localization of the Chlamydia trachomatis major outer membrane protein in Escherichia coli. Mol Microbiol. 1992 May;6(9):1087–1094. doi: 10.1111/j.1365-2958.1992.tb01545.x. [DOI] [PubMed] [Google Scholar]
  52. Koomey M., Gotschlich E. C., Robbins K., Bergström S., Swanson J. Effects of recA mutations on pilus antigenic variation and phase transitions in Neisseria gonorrhoeae. Genetics. 1987 Nov;117(3):391–398. doi: 10.1093/genetics/117.3.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Laga M., Manoka A., Kivuvu M., Malele B., Tuliza M., Nzila N., Goeman J., Behets F., Batter V., Alary M. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS. 1993 Jan;7(1):95–102. doi: 10.1097/00002030-199301000-00015. [DOI] [PubMed] [Google Scholar]
  54. Lagergård T., Purvén M. Neutralizing antibodies to Haemophilus ducreyi cytotoxin. Infect Immun. 1993 Apr;61(4):1589–1592. doi: 10.1128/iai.61.4.1589-1592.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Lamont H. C., Semine D. Z., Leveille C., Nichols R. L. Immunity to vaginal reinfection in female guinea pigs infected sexually with Chlamydia of guinea pig inclusion conjunctivitis. Infect Immun. 1978 Mar;19(3):807–813. doi: 10.1128/iai.19.3.807-813.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Legrain M., Mazarin V., Irwin S. W., Bouchon B., Quentin-Millet M. J., Jacobs E., Schryvers A. B. Cloning and characterization of Neisseria meningitidis genes encoding the transferrin-binding proteins Tbp1 and Tbp2. Gene. 1993 Aug 16;130(1):73–80. doi: 10.1016/0378-1119(93)90348-7. [DOI] [PubMed] [Google Scholar]
  57. Liu H., Alder J. D., Steiner B. M., Stein-Streilein J., Lim L., Schell R. F. Role of L3T4+ and 38+ T-cell subsets in resistance against infection with Treponema pallidum subsp. pertenue in hamsters. Infect Immun. 1991 Feb;59(2):529–536. doi: 10.1128/iai.59.2.529-536.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Liu H., Steiner B. M., Alder J. D., Baertschy D. K., Schell R. F. Immune T cells sorted by flow cytometry confer protection against infection with Treponema pallidum subsp. pertenue in hamsters. Infect Immun. 1990 Jun;58(6):1685–1690. doi: 10.1128/iai.58.6.1685-1690.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Lomholt H., Poulsen K., Caugant D. A., Kilian M. Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2120–2124. doi: 10.1073/pnas.89.6.2120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Lynch E. C., Blake M. S., Gotschlich E. C., Mauro A. Studies of Porins: Spontaneously Transferred from Whole Cells and Reconstituted from Purified Proteins of Neisseria gonorrhoeae and Neisseria meningitidis. Biophys J. 1984 Jan;45(1):104–107. doi: 10.1016/S0006-3495(84)84127-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. MAGNUSON H. J., THOMAS E. W., OLANSKY S., KAPLAN B. I., DE MELLO L., CUTLER J. C. Inoculation syphilis in human volunteers. Medicine (Baltimore) 1956 Feb;35(1):33–82. doi: 10.1097/00005792-195602000-00002. [DOI] [PubMed] [Google Scholar]
  62. Makino S., van Putten J. P., Meyer T. F. Phase variation of the opacity outer membrane protein controls invasion by Neisseria gonorrhoeae into human epithelial cells. EMBO J. 1991 Jun;10(6):1307–1315. doi: 10.1002/j.1460-2075.1991.tb07649.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Mandrell R. E., Griffiss J. M., Macher B. A. Lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis have components that are immunochemically similar to precursors of human blood group antigens. Carbohydrate sequence specificity of the mouse monoclonal antibodies that recognize crossreacting antigens on LOS and human erythrocytes. J Exp Med. 1988 Jul 1;168(1):107–126. doi: 10.1084/jem.168.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Mandrell R. E., Lesse A. J., Sugai J. V., Shero M., Griffiss J. M., Cole J. A., Parsons N. J., Smith H., Morse S. A., Apicella M. A. In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation. J Exp Med. 1990 May 1;171(5):1649–1664. doi: 10.1084/jem.171.5.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Martin D. H., Pollock S., Kuo C. C., Wang S. P., Brunham R. C., Holmes K. K. Chlamydia trachomatis infections in men with Reiter's syndrome. Ann Intern Med. 1984 Feb;100(2):207–213. doi: 10.7326/0003-4819-100-2-207. [DOI] [PubMed] [Google Scholar]
  66. McChesney D., Tramont E. C., Boslego J. W., Ciak J., Sadoff J., Brinton C. C. Genital antibody response to a parenteral gonococcal pilus vaccine. Infect Immun. 1982 Jun;36(3):1006–1012. doi: 10.1128/iai.36.3.1006-1012.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Metzger M., Smogór W. Artificial immunization of rabbits against syphilis. I. Effect of increasing doses of treponemes given by the intramuscular route. Br J Vener Dis. 1969 Dec;45(4):308–312. doi: 10.1136/sti.45.4.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Miller J. N. Immunity in experimental syphilis. VI. Successful vaccination of rabbits with Treponema pallidum, Nichols strain, attenuated by -irradiation. J Immunol. 1973 May;110(5):1206–1215. [PubMed] [Google Scholar]
  69. Morrison R. P., Belland R. J., Lyng K., Caldwell H. D. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. J Exp Med. 1989 Oct 1;170(4):1271–1283. doi: 10.1084/jem.170.4.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Morrison R. P., Lyng K., Caldwell H. D. Chlamydial disease pathogenesis. Ocular hypersensitivity elicited by a genus-specific 57-kD protein. J Exp Med. 1989 Mar 1;169(3):663–675. doi: 10.1084/jem.169.3.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Morse S. A. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev. 1989 Apr;2(2):137–157. doi: 10.1128/cmr.2.2.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Murdin A. D., Su H., Manning D. S., Klein M. H., Parnell M. J., Caldwell H. D. A poliovirus hybrid expressing a neutralization epitope from the major outer membrane protein of Chlamydia trachomatis is highly immunogenic. Infect Immun. 1993 Oct;61(10):4406–4414. doi: 10.1128/iai.61.10.4406-4414.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Norris S. J. Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologic roles. Treponema Pallidum Polypeptide Research Group. Microbiol Rev. 1993 Sep;57(3):750–779. doi: 10.1128/mr.57.3.750-779.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Ober W. B. Boswell's gonorrhea. Bull N Y Acad Med. 1969 Jun;45(6):587–636. [PMC free article] [PubMed] [Google Scholar]
  75. Patton D. L. Immunopathology and histopathology of experimental chlamydial salpingitis. Rev Infect Dis. 1985 Nov-Dec;7(6):746–753. doi: 10.1093/clinids/7.6.746. [DOI] [PubMed] [Google Scholar]
  76. Plummer F. A., Chubb H., Simonsen J. N., Bosire M., Slaney L., Maclean I., Ndinya-Achola J. O., Waiyaki P., Brunham R. C. Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection. J Clin Invest. 1993 Jan;91(1):339–343. doi: 10.1172/JCI116190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Plummer F. A., Simonsen J. N., Cameron D. W., Ndinya-Achola J. O., Kreiss J. K., Gakinya M. N., Waiyaki P., Cheang M., Piot P., Ronald A. R. Cofactors in male-female sexual transmission of human immunodeficiency virus type 1. J Infect Dis. 1991 Feb;163(2):233–239. doi: 10.1093/infdis/163.2.233. [DOI] [PubMed] [Google Scholar]
  78. Plummer F. A., Simonsen J. N., Chubb H., Slaney L., Kimata J., Bosire M., Ndinya-Achola J. O., Ngugi E. N. Epidemiologic evidence for the development of serovar-specific immunity after gonococcal infection. J Clin Invest. 1989 May;83(5):1472–1476. doi: 10.1172/JCI114040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Purvén M., Lagergård T. Haemophilus ducreyi, a cytotoxin-producing bacterium. Infect Immun. 1992 Mar;60(3):1156–1162. doi: 10.1128/iai.60.3.1156-1162.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Qu Z., Cheng X., de la Maza L. M., Peterson E. M. Characterization of a neutralizing monoclonal antibody directed at variable domain I of the major outer membrane protein of Chlamydia trachomatis C-complex serovars. Infect Immun. 1993 Apr;61(4):1365–1370. doi: 10.1128/iai.61.4.1365-1370.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. 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 Mar;86(6):2051–2055. doi: 10.1073/pnas.86.6.2051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Rank R. G., Soderberg L. S., Sanders M. M., Batteiger B. E. Role of cell-mediated immunity in the resolution of secondary chlamydial genital infection in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis. Infect Immun. 1989 Mar;57(3):706–710. doi: 10.1128/iai.57.3.706-710.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Reid R. H., Boedeker E. C., McQueen C. E., Davis D., Tseng L. Y., Kodak J., Sau K., Wilhelmsen C. L., Nellore R., Dalal P. Preclinical evaluation of microencapsulated CFA/II oral vaccine against enterotoxigenic E. coli. Vaccine. 1993;11(2):159–167. doi: 10.1016/0264-410x(93)90013-n. [DOI] [PubMed] [Google Scholar]
  84. Rice P. A., Vayo H. E., Tam M. R., Blake M. S. Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune serum. J Exp Med. 1986 Nov 1;164(5):1735–1748. doi: 10.1084/jem.164.5.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Ripa T. Epidemiologic control of genital Chlamydia trachomatis infections. Scand J Infect Dis Suppl. 1990;69:157–167. [PubMed] [Google Scholar]
  86. Robinson E. N., Jr, Clemens C. M., Schoolnik G. K., McGee Z. A. Probing the surface of Neisseria gonorrhoeae: immunoelectron microscopic studies to localize cyanogen bromide fragment 2 in gonococcal pili. Mol Microbiol. 1989 Jan;3(1):57–64. doi: 10.1111/j.1365-2958.1989.tb00104.x. [DOI] [PubMed] [Google Scholar]
  87. Rothbard J. B., Fernandez R., Wang L., Teng N. N., Schoolnik G. K. Antibodies to peptides corresponding to a conserved sequence of gonococcal pilins block bacterial adhesion. Proc Natl Acad Sci U S A. 1985 Feb;82(3):915–919. doi: 10.1073/pnas.82.3.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. 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 Sep;140(3):378–383. doi: 10.1093/infdis/140.3.378. [DOI] [PubMed] [Google Scholar]
  89. Segal E., Hagblom P., Seifert H. S., So M. Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2177–2181. doi: 10.1073/pnas.83.7.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Siegel M., Olsen D., Critchlow C., Buchanan T. M. Gonococcal pili: safety and immunogenicity in humans and antibody function in vitro. J Infect Dis. 1982 Mar;145(3):300–310. doi: 10.1093/infdis/145.3.300. [DOI] [PubMed] [Google Scholar]
  91. Simonsen J. N., Cameron D. W., Gakinya M. N., Ndinya-Achola J. O., D'Costa L. J., Karasira P., Cheang M., Ronald A. R., Piot P., Plummer F. A. Human immunodeficiency virus infection among men with sexually transmitted diseases. Experience from a center in Africa. N Engl J Med. 1988 Aug 4;319(5):274–278. doi: 10.1056/NEJM198808043190504. [DOI] [PubMed] [Google Scholar]
  92. Stamm W. E., Handsfield H. H., Rompalo A. M., Ashley R. L., Roberts P. L., Corey L. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. JAMA. 1988 Sep 9;260(10):1429–1433. [PubMed] [Google Scholar]
  93. Stephens R. S., Sanchez-Pescador R., Wagar E. A., Inouye C., Urdea M. S. Diversity of Chlamydia trachomatis major outer membrane protein genes. J Bacteriol. 1987 Sep;169(9):3879–3885. doi: 10.1128/jb.169.9.3879-3885.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Stephens R. S., Wagar E. A., Schoolnik G. K. High-resolution mapping of serovar-specific and common antigenic determinants of the major outer membrane protein of Chlamydia trachomatis. J Exp Med. 1988 Mar 1;167(3):817–831. doi: 10.1084/jem.167.3.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Stern A., Brown M., Nickel P., Meyer T. F. Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell. 1986 Oct 10;47(1):61–71. doi: 10.1016/0092-8674(86)90366-1. [DOI] [PubMed] [Google Scholar]
  96. Stevenson P., Williams P., Griffiths E. Common antigenic domains in transferrin-binding protein 2 of Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae type b. Infect Immun. 1992 Jun;60(6):2391–2396. doi: 10.1128/iai.60.6.2391-2396.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Sturm A. W. Comparison of antimicrobial susceptibility patterns of fifty-seven strains of Haemophilus ducreyi isolated in Amsterdam from 1978 to 1985. J Antimicrob Chemother. 1987 Feb;19(2):187–191. doi: 10.1093/jac/19.2.187. [DOI] [PubMed] [Google Scholar]
  98. Su H., Caldwell H. D. Immunogenicity of a chimeric peptide corresponding to T helper and B cell epitopes of the Chlamydia trachomatis major outer membrane protein. J Exp Med. 1992 Jan 1;175(1):227–235. doi: 10.1084/jem.175.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Su H., Morrison R. P., Watkins N. G., Caldwell H. D. Identification and characterization of T helper cell epitopes of the major outer membrane protein of Chlamydia trachomatis. J Exp Med. 1990 Jul 1;172(1):203–212. doi: 10.1084/jem.172.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Su H., Zhang Y. X., Barrera O., Watkins N. G., Caldwell H. D. Differential effect of trypsin on infectivity of Chlamydia trachomatis: loss of infectivity requires cleavage of major outer membrane protein variable domains II and IV. Infect Immun. 1988 Aug;56(8):2094–2100. doi: 10.1128/iai.56.8.2094-2100.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Sugasawara R. J., Cannon J. G., Black W. J., Nachamkin I., Sweet R. L., Brooks G. F. Inhibition of Neisseria gonorrhoeae attachment to HeLa cells with monoclonal antibody directed against a protein II. Infect Immun. 1983 Dec;42(3):980–985. doi: 10.1128/iai.42.3.980-985.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Swanson J., Barrera O., Sola J., Boslego J. Expression of outer membrane protein II by gonococci in experimental gonorrhea. J Exp Med. 1988 Dec 1;168(6):2121–2129. doi: 10.1084/jem.168.6.2121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Swanson J., Robbins K., Barrera O., Corwin D., Boslego J., Ciak J., Blake M., Koomey J. M. Gonococcal pilin variants in experimental gonorrhea. J Exp Med. 1987 May 1;165(5):1344–1357. doi: 10.1084/jem.165.5.1344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Taylor H. R., Maclean I. W., Brunham R. C., Pal S., Whittum-Hudson J. Chlamydial heat shock proteins and trachoma. Infect Immun. 1990 Sep;58(9):3061–3063. doi: 10.1128/iai.58.9.3061-3063.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. 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 May;85(10):3608–3612. doi: 10.1073/pnas.85.10.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Toth M., Jeremias J., Ledger W. J., Witkin S. S. In vivo tumor necrosis factor production in women with salpingitis. Surg Gynecol Obstet. 1992 May;174(5):359–362. [PubMed] [Google Scholar]
  107. Toye B., Laferrière C., Claman P., Jessamine P., Peeling R. Association between antibody to the chlamydial heat-shock protein and tubal infertility. J Infect Dis. 1993 Nov;168(5):1236–1240. doi: 10.1093/infdis/168.5.1236. [DOI] [PubMed] [Google Scholar]
  108. Toye B., Zhong G. M., Peeling R., Brunham R. C. Immunologic characterization of a cloned fragment containing the species-specific epitope from the major outer membrane protein of Chlamydia trachomatis. Infect Immun. 1990 Dec;58(12):3909–3913. doi: 10.1128/iai.58.12.3909-3913.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  109. Tuffrey M., Alexander F., Conlan W., Woods C., Ward M. Heterotypic protection of mice against chlamydial salpingitis and colonization of the lower genital tract with a human serovar F isolate of Chlamydia trachomatis by prior immunization with recombinant serovar L1 major outer-membrane protein. J Gen Microbiol. 1992 Aug;138(Pt 8):1707–1715. doi: 10.1099/00221287-138-8-1707. [DOI] [PubMed] [Google Scholar]
  110. Virji M., Fletcher J. N., Zak K., Heckels J. E. The potential protective effect of monoclonal antibodies to gonococcal outer membrane protein IA. J Gen Microbiol. 1987 Sep;133(9):2639–2646. doi: 10.1099/00221287-133-9-2639. [DOI] [PubMed] [Google Scholar]
  111. Virji M., Heckels J. E. Role of anti-pilus antibodies in host defense against gonococcal infection studied with monoclonal anti-pilus antibodies. Infect Immun. 1985 Sep;49(3):621–628. doi: 10.1128/iai.49.3.621-628.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Virji M., Heckels J. E. The role of common and type-specific pilus antigenic domains in adhesion and virulence of gonococci for human epithelial cells. J Gen Microbiol. 1984 May;130(5):1089–1095. doi: 10.1099/00221287-130-5-1089. [DOI] [PubMed] [Google Scholar]
  113. Virji M., Zak K., Heckels J. E. Monoclonal antibodies to gonococcal outer membrane protein IB: use in investigation of the potential protective effect of antibodies directed against conserved and type-specific epitopes. J Gen Microbiol. 1986 Jun;132(6):1621–1629. doi: 10.1099/00221287-132-6-1621. [DOI] [PubMed] [Google Scholar]
  114. Wagar E. A., Schachter J., Bavoil P., Stephens R. S. Differential human serologic response to two 60,000 molecular weight Chlamydia trachomatis antigens. J Infect Dis. 1990 Oct;162(4):922–927. doi: 10.1093/infdis/162.4.922. [DOI] [PubMed] [Google Scholar]
  115. 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 Sep;171(9):5005–5011. doi: 10.1128/jb.171.9.5005-5011.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Ward M. E. Chlamydial vaccines--future trends. J Infect. 1992 Jul;25 (Suppl 1):11–26. doi: 10.1016/0163-4453(92)91882-c. [DOI] [PubMed] [Google Scholar]
  117. Watkins N. G., Hadlow W. J., Moos A. B., Caldwell H. D. Ocular delayed hypersensitivity: a pathogenetic mechanism of chlamydial-conjunctivitis in guinea pigs. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7480–7484. doi: 10.1073/pnas.83.19.7480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Wetzler L. M., Barry K., Blake M. S., Gotschlich E. C. Gonococcal lipooligosaccharide sialylation prevents complement-dependent killing by immune sera. Infect Immun. 1992 Jan;60(1):39–43. doi: 10.1128/iai.60.1.39-43.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  119. Wetzler L. M., Blake M. S., Barry K., Gotschlich E. C. Gonococcal porin vaccine evaluation: comparison of Por proteosomes, liposomes, and blebs isolated from rmp deletion mutants. J Infect Dis. 1992 Sep;166(3):551–555. doi: 10.1093/infdis/166.3.551. [DOI] [PubMed] [Google Scholar]
  120. Wetzler L. M., Blake M. S., Gotschlich E. C. Characterization and specificity of antibodies to protein I of Neisseria gonorrhoeae produced by injection with various protein I-adjuvant preparations. J Exp Med. 1988 Nov 1;168(5):1883–1897. doi: 10.1084/jem.168.5.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Wicher K., Schouls L. M., Wicher V., Van Embden J. D., Nakeeb S. S. Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols. Infect Immun. 1991 Dec;59(12):4343–4348. doi: 10.1128/iai.59.12.4343-4348.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Wicher V., Zabek J., Wicher K. Pathogen-specific humoral response in Treponema pallidum-infected humans, rabbits, and guinea pigs. J Infect Dis. 1991 Apr;163(4):830–836. [PubMed] [Google Scholar]
  123. Wolner-Hanssen P., Patton D. L., Holmes K. K. Protective immunity in pig-tailed macaques after cervical infection with Chlamydia trachomatis. Sex Transm Dis. 1991 Jan-Mar;18(1):21–25. doi: 10.1097/00007435-199101000-00005. [DOI] [PubMed] [Google Scholar]
  124. Yuan Y., Zhang Y. X., Watkins N. G., Caldwell H. D. Nucleotide and deduced amino acid sequences for the four variable domains of the major outer membrane proteins of the 15 Chlamydia trachomatis serovars. Infect Immun. 1989 Apr;57(4):1040–1049. doi: 10.1128/iai.57.4.1040-1049.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  125. Zhang Y. X., Stewart S. J., Caldwell H. D. Protective monoclonal antibodies to Chlamydia trachomatis serovar- and serogroup-specific major outer membrane protein determinants. Infect Immun. 1989 Feb;57(2):636–638. doi: 10.1128/iai.57.2.636-638.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Zhang Y. X., Stewart S., Joseph T., Taylor H. R., Caldwell H. D. Protective monoclonal antibodies recognize epitopes located on the major outer membrane protein of Chlamydia trachomatis. J Immunol. 1987 Jan 15;138(2):575–581. [PubMed] [Google Scholar]
  127. Zhong G., Brunham R. C. Antibody responses to the chlamydial heat shock proteins hsp60 and hsp70 are H-2 linked. Infect Immun. 1992 Aug;60(8):3143–3149. doi: 10.1128/iai.60.8.3143-3149.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  128. van Putten J. P. Phase variation of lipopolysaccharide directs interconversion of invasive and immuno-resistant phenotypes of Neisseria gonorrhoeae. EMBO J. 1993 Nov;12(11):4043–4051. doi: 10.1002/j.1460-2075.1993.tb06088.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  129. van der Ley P., Heckels J. E., Virji M., Hoogerhout P., Poolman J. T. Topology of outer membrane porins in pathogenic Neisseria spp. Infect Immun. 1991 Sep;59(9):2963–2971. doi: 10.1128/iai.59.9.2963-2971.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

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