Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Dec;64(12):5341–5348. doi: 10.1128/iai.64.12.5341-5348.1996

Intranasal immunization induces long-term protection in mice against a Chlamydia trachomatis genital challenge.

S Pal 1, E M Peterson 1, L M de la Maza 1
PMCID: PMC174528  PMID: 8945586

Abstract

In an attempt to confer long-term protective immunity, BALB/c female mice were immunized intranasally with 10(4) inclusion-forming units (IFU) of the Chlamydia trachomatis mouse pneumonitis biovar (MoPn). Animals were subsequently challenged in the ovarian bursa with 10(5) C. trachomatis MoPn IFU at 60, 120, or 180 days post-intranasal immunization. Two control groups were included in the study. One control was sham immunized and mock challenged, and another group was sham immunized and challenged with 10(5) C. trachomatis MoPn IFU. Vaginal cultures were collected at regular intervals following the intrabursal challenge. In comparison with the sham-immunized mice, the animals that were intranasally immunized with C. trachomatis had significant protection, as shown by a reduction in the number of animals that had positive vaginal cultures and by a decrease in the intensity and length of the shedding. Furthermore, histopathological characterization of the genital tract following challenge, in the three groups of mice, showed a minimal inflammatory infiltrate in the C. trachomatis-immunized animals, when compared with the sham-immunized control group. Subsequently, the three groups of female mice that were challenged at 60, 120 and 180 days postimmunization were mated at 6 weeks following the challenge. Overall, in the mice intranasally immunized with C. trachomatis the fertility rates and the number of embryos were similar to those in the sham-immunized and mock-challenged group. In contrast, there was a significant increase in infertility in the groups of mice that were sham immunized and C. trachomatis challenged. In conclusion, intranasal immunization with C. trachomatis induces long-term protection against a genital challenge as shown by a decrease in the infection and infertility rates when compared with sham-immunized animals. Thus, this model may help to characterize the parameters of the immune response that are important in maintaining long-term protection and may aid in identifying the antigenic determinants involved in eliciting protection.

Full Text

The Full Text of this article is available as a PDF (243.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Chow J. M., Yonekura M. L., Richwald G. A., Greenland S., Sweet R. L., Schachter J. The association between Chlamydia trachomatis and ectopic pregnancy. A matched-pair, case-control study. JAMA. 1990 Jun 20;263(23):3164–3167. [PubMed] [Google Scholar]
  6. Coles A. M., Crosby H. A., Pearce J. H. Analysis of the human serological response to Chlamydia trachomatis 60-kDa proteins by two-dimensional electrophoresis and immunoblotting. FEMS Microbiol Lett. 1991 Jul 1;65(3):299–303. doi: 10.1016/0378-1097(91)90231-x. [DOI] [PubMed] [Google Scholar]
  7. Cui Z. D., Tristram D., LaScolea L. J., Kwiatkowski T., Jr, Kopti S., Ogra P. L. Induction of antibody response to Chlamydia trachomatis in the genital tract by oral immunization. Infect Immun. 1991 Apr;59(4):1465–1469. doi: 10.1128/iai.59.4.1465-1469.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. GRAYSTON J. T., WANG S. P., YANG Y. F., WOOLRIDGE R. L. The effect of trachoma virus vaccine on the course of experimental trachoma infection in blind human volunteers. J Exp Med. 1962 May 1;115:1009–1022. doi: 10.1084/jem.115.5.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. Jones R. B., Ardery B. R., Hui S. L., Cleary R. E. Correlation between serum antichlamydial antibodies and tubal factor as a cause of infertility. Fertil Steril. 1982 Nov;38(5):553–558. doi: 10.1016/s0015-0282(16)46634-3. [DOI] [PubMed] [Google Scholar]
  14. Landers D. V., Erlich K., Sung M., Schachter J. Role of L3T4-bearing T-cell populations in experimental murine chlamydial salpingitis. Infect Immun. 1991 Oct;59(10):3774–3777. doi: 10.1128/iai.59.10.3774-3777.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mestecky J. The common mucosal immune system and current strategies for induction of immune responses in external secretions. J Clin Immunol. 1987 Jul;7(4):265–276. doi: 10.1007/BF00915547. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. 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]
  19. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  20. Murray E. S., Charbonnet L. T., MacDonald A. B. Immunity to chlamydial infections of the eye. I. The role of circulatory and secretory antibodies in resistance to reinfection with guinea pig inclusion conjunctivitis. J Immunol. 1973 Jun;110(6):1518–1525. [PubMed] [Google Scholar]
  21. Nichols R. L., Murray E. S., Nisson P. E. Use of enteric vaccines in protection against chlamydial infections of the genital tract and the eye of guinea pigs. J Infect Dis. 1978 Dec;138(6):742–746. doi: 10.1093/infdis/138.6.742. [DOI] [PubMed] [Google Scholar]
  22. Paavonen J., Lähdeaho M. L., Puolakkainen M., Mäki M., Parkkonen P., Lehtinen M. Antibody response to B cell epitopes of Chlamydia trachomatis 60-kDa heat-shock protein and corresponding mycobacterial and human peptides in infants with chlamydial pneumonitis. J Infect Dis. 1994 Apr;169(4):908–911. doi: 10.1093/infdis/169.4.908. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]
  26. 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]
  27. Peterson E. M., Oda R., Tse P., Gastaldi C., Stone S. C., de la Maza L. M. Comparison of a single-antigen microimmunofluorescence assay and inclusion fluorescent-antibody assay for detecting chlamydial antibodies and correlation of the results with neutralizing ability. J Clin Microbiol. 1989 Feb;27(2):350–352. doi: 10.1128/jcm.27.2.350-352.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Ramsey K. H., Newhall W. J., 5th, Rank R. G. Humoral immune response to chlamydial genital infection of mice with the agent of mouse pneumonitis. Infect Immun. 1989 Aug;57(8):2441–2446. doi: 10.1128/iai.57.8.2441-2446.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. Rank R. G., Batteiger B. E., Soderberg L. S. Immunization against chlamydial genital infection in guinea pigs with UV-inactivated and viable chlamydiae administered by different routes. Infect Immun. 1990 Aug;58(8):2599–2605. doi: 10.1128/iai.58.8.2599-2605.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Sedgwick J. D., Holt P. G. A solid-phase immunoenzymatic technique for the enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Feb 25;57(1-3):301–309. doi: 10.1016/0022-1759(83)90091-1. [DOI] [PubMed] [Google Scholar]
  37. Svensson L., Mårdh P. A., Ahlgren M., Nordenskjöld F. Ectopic pregnancy and antibodies to Chlamydia trachomatis. Fertil Steril. 1985 Sep;44(3):313–317. [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. 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]
  41. 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]
  42. 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]
  43. Weström L., Mårdh P. A. Chlamydial salpingitis. Br Med Bull. 1983 Apr;39(2):145–150. doi: 10.1093/oxfordjournals.bmb.a071806. [DOI] [PubMed] [Google Scholar]
  44. Zhong G. M., Peterson E. M., Czarniecki C. W., Schreiber R. D., de la Maza L. M. Role of endogenous gamma interferon in host defense against Chlamydia trachomatis infections. Infect Immun. 1989 Jan;57(1):152–157. doi: 10.1128/iai.57.1.152-157.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. 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]
  47. de la Maza L. M., Plunkett M. J., Carlson E. J., Peterson E. M., Czarniecki C. W. Ultrastructural analysis of the anti-chlamydial activity of recombinant murine interferon-gamma. Exp Mol Pathol. 1987 Aug;47(1):13–25. doi: 10.1016/0014-4800(87)90003-7. [DOI] [PubMed] [Google Scholar]
  48. 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]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES