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. 1997 Aug;65(8):3361–3369. doi: 10.1128/iai.65.8.3361-3369.1997

Immunization with an acellular vaccine consisting of the outer membrane complex of Chlamydia trachomatis induces protection against a genital challenge.

S Pal 1, I Theodor 1, E M Peterson 1, L M de la Maza 1
PMCID: PMC175475  PMID: 9234798

Abstract

The ability to induce protection against a genital challenge was studied in BALB/c female mice with three Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) preparations as well as an acellular vaccine consisting of the chlamydial outer membrane complex (COMC). The MOMP preparations were extracted with three different types of detergents, sodium dodecyl sulfate (SDS), n-octyl-beta-D-glucopyranoside (OGP), and Zwittergent 3-14 (Z3-14). A positive immunization control consisted of mice inoculated intranasally with 10(4) C. trachomatis MoPn inclusion-forming units (IFU). Mice inoculated with ovalbumin served as a negative control. Furthermore, a sham-immunized, nonchallenged group was included as a fertility control. Two weeks after the last immunization, the mice were challenged in the left ovarian bursa with 10(5) C. trachomatis MoPn IFU. Vaginal swabs were collected for culture, vaginal and serum samples were assayed for chlamydial-specific antibodies, and splenocytes were collected to determine the lymphoproliferative response. At 42 days after the challenge, the mice were mated with proven male breeder mice. Animals that were considered to be pregnant (as determined by weight) were killed, and the embryos were counted. A significant humoral and cell-mediated immune response was observed in all the groups of mice inoculated with chlamydial antigens. Antibodies to variable domain (VD)1 of the MOMP were detected in serum samples from all the immunized groups. However, antibodies to VD3 and VD4 were detected only in the groups immunized with the Z3-14-MOMP and the COMC. Mice immunized with COMC developed significant immunoglobulin A chlamydia-specific antibodies in the vagina, while mice immunized with the detergent-extracted MOMPs had low antibody titers. Following the intrabursal challenge, a significant decrease in the intensity and duration of vaginal shedding was noted in the mice immunized with COMC and a moderate decrease was noted in the group immunized with OGP-MOMP. No protection against the infection was noted in the groups of animals immunized with SDS- and Z3-14-MOMP. Furthermore, of the mice immunized with the COMC preparation, only 25% (4 of 20) shed C. trachomatis, as determined by vaginal culture, while 83% (40 of 48) of the control mice inoculated with ovalbumin were culture positive (P < 0.05). In addition, after mating, the mice inoculated with COMC were found to have fertility rates comparable to those of the control sham-immunized, nonchallenged animals (70% [14 of 20] versus 81% [17 of 21], respectively [P > 0.05]), and there were no significant differences between the average number of embryos per mouse in the two groups (5.1 versus 5.9, respectively [P > 0.05]). In contrast, mice immunized with the purified MOMP preparations were not protected against infertility. In summary, a preparation of the COMC protected mice against infection and infertility, supporting the feasibility of the development of an acellular vaccine against C. trachomatis infections.

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Selected References

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  1. Batteiger B. E., Rank R. G., Bavoil P. M., Soderberg L. S. Partial protection against genital reinfection by immunization of guinea-pigs with isolated outer-membrane proteins of the chlamydial agent of guinea-pig inclusion conjunctivitis. J Gen Microbiol. 1993 Dec;139(12):2965–2972. doi: 10.1099/00221287-139-12-2965. [DOI] [PubMed] [Google Scholar]
  2. Bavoil P., Ohlin A., Schachter J. Role of disulfide bonding in outer membrane structure and permeability in Chlamydia trachomatis. Infect Immun. 1984 May;44(2):479–485. doi: 10.1128/iai.44.2.479-485.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brunham R. C., Binns B., McDowell J., Paraskevas M. Chlamydia trachomatis infection in women with ectopic pregnancy. Obstet Gynecol. 1986 May;67(5):722–726. doi: 10.1097/00006250-198605000-00022. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Brunham R. C., Maclean I. W., Binns B., Peeling R. W. Chlamydia trachomatis: its role in tubal infertility. J Infect Dis. 1985 Dec;152(6):1275–1282. doi: 10.1093/infdis/152.6.1275. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Caldwell H. D., Kromhout J., Schachter J. Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis. Infect Immun. 1981 Mar;31(3):1161–1176. doi: 10.1128/iai.31.3.1161-1176.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Caldwell H. D., Schachter J. Antigenic analysis of the major outer membrane protein of Chlamydia spp. Infect Immun. 1982 Mar;35(3):1024–1031. doi: 10.1128/iai.35.3.1024-1031.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cates W., Jr, Rolfs R. T., Jr, Aral S. O. Sexually transmitted diseases, pelvic inflammatory disease, and infertility: an epidemiologic update. Epidemiol Rev. 1990;12:199–220. doi: 10.1093/oxfordjournals.epirev.a036054. [DOI] [PubMed] [Google Scholar]
  10. Fielder T. J., Pal S., Peterson E. M., de la Maza L. M. Sequence of the gene encoding the major outer membrane protein of the mouse pneumonitis biovar of Chlamydia trachomatis. Gene. 1991 Sep 30;106(1):137–138. doi: 10.1016/0378-1119(91)90579-z. [DOI] [PubMed] [Google Scholar]
  11. Fitch W. M., Peterson E. M., de la Maza L. M. Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development. Mol Biol Evol. 1993 Jul;10(4):892–913. doi: 10.1093/oxfordjournals.molbev.a040048. [DOI] [PubMed] [Google Scholar]
  12. Geysen H. M., Rodda S. J., Mason T. J., Tribbick G., Schoofs P. G. Strategies for epitope analysis using peptide synthesis. J Immunol Methods. 1987 Sep 24;102(2):259–274. doi: 10.1016/0022-1759(87)90085-8. [DOI] [PubMed] [Google Scholar]
  13. Grayston J. T., Wang S. P. The potential for vaccine against infection of the genital tract with Chlamydia trachomatis. Sex Transm Dis. 1978 Apr-Jun;5(2):73–77. doi: 10.1097/00007435-197804000-00011. [DOI] [PubMed] [Google Scholar]
  14. Grayston J. T., Wang S. New knowledge of chlamydiae and the diseases they cause. J Infect Dis. 1975 Jul;132(1):87–105. doi: 10.1093/infdis/132.1.87. [DOI] [PubMed] [Google Scholar]
  15. Igietseme J. U., Ramsey K. H., Magee D. M., Williams D. M., Kincy T. J., Rank R. G. Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone. Reg Immunol. 1993 Nov-Dec;5(6):317–324. [PubMed] [Google Scholar]
  16. Morrison R. P., Feilzer K., Tumas D. B. Gene knockout mice establish a primary protective role for major histocompatibility complex class II-restricted responses in Chlamydia trachomatis genital tract infection. Infect Immun. 1995 Dec;63(12):4661–4668. doi: 10.1128/iai.63.12.4661-4668.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pal S., Cheng X., Peterson E. M., de la Maza L. M. Mapping of a surface-exposed B-cell epitope to the variable sequent 3 of the major outer-membrane protein of Chlamydia trachomatis. J Gen Microbiol. 1993 Jul;139(7):1565–1570. doi: 10.1099/00221287-139-7-1565. [DOI] [PubMed] [Google Scholar]
  18. Pal S., Fielder T. J., Peterson E. M., de la Maza L. M. Analysis of the immune response in mice following intrauterine infection with the Chlamydia trachomatis mouse pneumonitis biovar. Infect Immun. 1993 Feb;61(2):772–776. doi: 10.1128/iai.61.2.772-776.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pal S., Fielder T. J., Peterson E. M., de la Maza L. M. Protection against infertility in a BALB/c mouse salpingitis model by intranasal immunization with the mouse pneumonitis biovar of Chlamydia trachomatis. Infect Immun. 1994 Aug;62(8):3354–3362. doi: 10.1128/iai.62.8.3354-3362.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pal S., Theodor I., Peterson E. M., de la Maza L. M. Monoclonal immunoglobulin A antibody to the major outer membrane protein of the Chlamydia trachomatis mouse pneumonitis biovar protects mice against a chlamydial genital challenge. Vaccine. 1997 Apr;15(5):575–582. doi: 10.1016/s0264-410x(97)00206-5. [DOI] [PubMed] [Google Scholar]
  21. Pavia C. S., Schachter J. Failure to detect cell-mediated cytotoxicity against Chlamydia trachomatis-infected cells. Infect Immun. 1983 Mar;39(3):1271–1274. doi: 10.1128/iai.39.3.1271-1274.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Peterson E. M., Cheng X., Markoff B. A., Fielder T. J., de la Maza L. M. Functional and structural mapping of Chlamydia trachomatis species-specific major outer membrane protein epitopes by use of neutralizing monoclonal antibodies. Infect Immun. 1991 Nov;59(11):4147–4153. doi: 10.1128/iai.59.11.4147-4153.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peterson E. M., Zhong G. M., Carlson E., de la Maza L. M. Protective role of magnesium in the neutralization by antibodies of Chlamydia trachomatis infectivity. Infect Immun. 1988 Apr;56(4):885–891. doi: 10.1128/iai.56.4.885-891.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Punnonen R., Terho P., Nikkanen V., Meurman O. Chlamydial serology in infertile women by immunofluorescence. Fertil Steril. 1979 Jun;31(6):656–659. doi: 10.1016/s0015-0282(16)44056-2. [DOI] [PubMed] [Google Scholar]
  25. Ramsey K. H., Rank R. G. Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines. Infect Immun. 1991 Mar;59(3):925–931. doi: 10.1128/iai.59.3.925-931.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ramsey K. H., Soderberg L. S., Rank R. G. Resolution of chlamydial genital infection in B-cell-deficient mice and immunity to reinfection. Infect Immun. 1988 May;56(5):1320–1325. doi: 10.1128/iai.56.5.1320-1325.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Roizman B. Introduction: objectives of herpes simplex virus vaccines seen from a historical perspective. Rev Infect Dis. 1991 Nov-Dec;13 (Suppl 11):S892–S894. doi: 10.1093/clind/13.supplement_11.s892. [DOI] [PubMed] [Google Scholar]
  28. Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
  29. Starnbach M. N., Bevan M. J., Lampe M. F. Protective cytotoxic T lymphocytes are induced during murine infection with Chlamydia trachomatis. J Immunol. 1994 Dec 1;153(11):5183–5189. [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Su H., Parnell M., Caldwell H. D. Protective efficacy of a parenterally administered MOMP-derived synthetic oligopeptide vaccine in a murine model of Chlamydia trachomatis genital tract infection: serum neutralizing IgG antibodies do not protect against chlamydial genital tract infection. Vaccine. 1995 Aug;13(11):1023–1032. doi: 10.1016/0264-410x(95)00017-u. [DOI] [PubMed] [Google Scholar]
  33. Swenson C. E., Schachter J. Infertility as a consequence of chlamydial infection of the upper genital tract in female mice. Sex Transm Dis. 1984 Apr-Jun;11(2):64–67. doi: 10.1097/00007435-198404000-00002. [DOI] [PubMed] [Google Scholar]
  34. Tan T. W., Herring A. J., Anderson I. E., Jones G. E. Protection of sheep against Chlamydia psittaci infection with a subcellular vaccine containing the major outer membrane protein. Infect Immun. 1990 Sep;58(9):3101–3108. doi: 10.1128/iai.58.9.3101-3108.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Taylor H. R., Whittum-Hudson J., Schachter J., Caldwell H. D., Prendergast R. A. Oral immunization with chlamydial major outer membrane protein (MOMP). Invest Ophthalmol Vis Sci. 1988 Dec;29(12):1847–1853. [PubMed] [Google Scholar]
  36. 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]
  37. Washington A. E., Aral S. O., Wølner-Hanssen P., Grimes D. A., Holmes K. K. Assessing risk for pelvic inflammatory disease and its sequelae. JAMA. 1991 Nov 13;266(18):2581–2586. [PubMed] [Google Scholar]
  38. Washington A. E., Katz P. Cost of and payment source for pelvic inflammatory disease. Trends and projections, 1983 through 2000. JAMA. 1991 Nov 13;266(18):2565–2569. [PubMed] [Google Scholar]
  39. Weström L., Joesoef R., Reynolds G., Hagdu A., Thompson S. E. Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis. 1992 Jul-Aug;19(4):185–192. [PubMed] [Google Scholar]
  40. 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]
  41. de la Maza L. M., Pal S., Khamesipour A., Peterson E. M. Intravaginal inoculation of mice with the Chlamydia trachomatis mouse pneumonitis biovar results in infertility. Infect Immun. 1994 May;62(5):2094–2097. doi: 10.1128/iai.62.5.2094-2097.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. de la Maza M. A., de la Maza L. M. A new computer model for estimating the impact of vaccination protocols and its application to the study of Chlamydia trachomatis genital infections. Vaccine. 1995 Jan;13(1):119–127. doi: 10.1016/0264-410x(95)80022-6. [DOI] [PubMed] [Google Scholar]

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