Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Oral immunization with an anti–idiotypic antibody to the exoglycolipid antigen protects against experimental Chlamydia trachomatis infection

Nature Medicine volume 2, pages 1116–1121 (1996)Cite this article

Abstract

Chlamydia trachomatis is the leading cause worldwide of preventable infectious blindness (trachoma) and sexually transmitted disease, including nongonoccocal urethritis and pelvic inflammatory disease. To date, no effective vaccine against C. trachomatis infection has been identified. A monoclonal anti–idiotypic antibody (anti–Id) to the chlamydial exoglycolipid antigen (GLXA) was tested in a murine model of ocular chlamydial infection for its ability to induce systemic immunity, which reduces microbiologic and clinical disease. The anti–Id to GLXA, delivered either systemically in soluble form or orally after encapsulation in poly(lactide) microspheres, induced significant protective immunity against ocular challenge of mice with a human biovar of C. trachomatis. Protection was associated with induction of anti–GLXA antibody and anti–chlamydial neutralizing antibody.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Schachter, J. & Dawson, C.R. The epidemiology of trachoma predicts more blindness in the future. Scand. J. Infect. Dis. 69 (Suppl.), 55–62 (1990).

    CAS  Google Scholar 

  2. Piot, P. Van den Hoek, A.R., Van Damme, L. & Laga, M. Epidemiology and control of genital chlamydial infections. in Chlamydial Infections, (eds. Orfila, J. et al) 7–15 (Societa Editrice Esculapio, Bologna, 1994).

    Google Scholar 

  3. Taylor, H.R. et al. An animal model of trachoma. II. The importance of repeated reinfection. Invest. Ophthalmol. Vis. ScL 23, 507–515 (1982).

    Google Scholar 

  4. Weström, L. & Wölner-Hanssen, P. Pathogenesis of pelvic inflammatory disease. Genitourin. Med. 69, 9–17 (1993).

    PubMed  PubMed Central  Google Scholar 

  5. Stephens, R.S., Wagar, E. & Schoolnik, G. High resolution mapping of serovar-specific and common antigenic determinants of the major outer membrane protein of Chlamydia trachomatis. J. Exp. Med. 167, 817–831 (1988).

    Article  CAS  Google Scholar 

  6. Newhall, W.J.V., Batteiger, B. & Jones, R.B. Analysis of human serological responses to proteins of Chlamydia trachomatis. Infect. Immun. 38, 1181–1189 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Wagar, E.A., Schachter, J., Bavoil, P. & Stephens, R.S. Differential human sero-logic response to two 60,000 molecular weight Chlamydia trachomatis antigens. J. Infect. Dis. 162, 922–927 (1990).

    Article  CAS  Google Scholar 

  8. Ting, L., Hsia, R., Haidaris, C.G. & Bavoil, P.M. Interaction of outer envelope proteins of Chlamydia psittaci GPIC with the HeLa cell surface. Infect. Immun. 63, 3600–3608 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Brunham, R.C. et al. Post-abortal Chlamydia trachomatis salpingitis: Correlating risk with antigen-specific responses and with neutralization. J. Infect. Dis. 155, 749–755 (1987).

    Article  CAS  Google Scholar 

  10. Campos, M. et al. An extract of the major outer membrane protein of Chlamydia trachomatis as a trachoma vaccine candidate. Invest. Ophthalmol. Vis. Sci 36, 1477–1491 (1995).

    CAS  PubMed  Google Scholar 

  11. Batteiger, B.E., Rank, R.G., Bavoil, P.M. & Soderberg, L.S.F. Partial protection against genital reinfection by immunization of guinea pigs with isolated outer membrane proteins of the chlamydial agent guinea pig inclusion conjunctivitis. J. Gen. Microbiol 139, 2965–2972 (1993).

    Article  CAS  Google Scholar 

  12. An, L.L. Production and characterization of anti-idiotypic antibodies, biological mimicry of a glycolipid exoantigen of Chlamydia trachomatis in vivo. Ph.D. dissertation, Univ. Massachusetts, Amherst (1993).

  13. Stuart, E.S. & MacDonald, A.B. Identification of two fatty acids in a group determinant of Chlamydia trachomatis. Curr. Microbiol. 11, 123–128 (1984).

    Article  CAS  Google Scholar 

  14. Stuart, E.S., Wyrick, P.B., Choong, J., Stoler, S.B. & MacDonald, A.B. Examination of chlamydial glycolipid with monoclonal antibodies: Cellular distribution and epitope binding. Immunology 74, 740–747 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Stuart, E.S., Tirrell, S.M. & MacDonald, A.B. Characterization of an antigen secreted by chlamydial infected cell culture. Immunology 61, 527–533 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Wyrick, P. et al. Chlamydia trachomatis antigens on the surface of human endometrial cells. Immunol. Infect. Dis. 4, 131–141 (1994).

    Google Scholar 

  17. Stuart, E.S., Troidle, K.M. & MacDonald, A.B. Chlamydial glycolipid antigen: Extracellular accumulation, biological activity, and antibody recognition. Curr. Microbiol. 28, 85–90 (1994).

    Article  CAS  Google Scholar 

  18. Stuart, E.S. & MacDonald, A.B. Some characteristics of a secreted chlamydial antigen recognized by IgG from Chlamydia trachomatis patient sera. Immunology 68, 469–473 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Schachter, J. Overview of Chlamydia trachomatis infection and the requirements for a vaccine. Rev. Infect. Dis. 7, 713–716 (1985).

    Article  CAS  Google Scholar 

  20. Michalek, S.M. et al. The IgA response: Inductive aspects, regulatory cells, and effector functions. Ann. N.Y. Acad. Sci. 409, 48–71 (1983).

    Article  CAS  Google Scholar 

  21. Pal, S., Pu, Z., Huneke, R.B., Taylor, H.R. & Whittum-Hudson, J.A. Chlamydia-specific lymphocytes in conjunctiva during ocular infection: Limiting dilution analysis. Reg. Immunol 3, 171–176 (1990).

    PubMed  Google Scholar 

  22. Rank, R.G. & Sanders, M.M. Pathogenesis of endometritis and salpingitis in a guinea pig model of chlamydial genital infection. Am. J. Pathol. 140, 927–936 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Reacher, M.H., Péer, J., Rapoza, P.A., Whittum-Hudson, J.A. & Taylor, H.R. T-cells and trachoma: Their role in cicatricial disease. Ophthalmology 98, 334–341 (1991).

    Article  CAS  Google Scholar 

  24. Cain, T.K. & Rank, R.G. Local Th1-like responses are induced by intravaginal infection of mice with the mouse pneumonitis biovar of Chlamydia trachomatis. Infect. Immun. 63, 516–521 (1995).

    Google Scholar 

  25. Su, H. & Caldwell, H.D. CD4+ T cells play a significant role in adoptive immunity to Chlamydia trachomatis infection of the mouse genital tract. Infect. Immun. 63, 3302–3308 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Rolf, J.M., Gaudin, H.M., Tirrell, S.M., MacDonald, A.B. & Eidels, L. Anti-idiotypic antibodies that protect cells against the action of diphtheria toxin. Proc. Natl. Acad. Sci. USA 86, 2036–2039 (1989).

    Article  CAS  Google Scholar 

  27. Nisonoff, A. & La Moyi, E. Implications of the presence of an internal image of the antigen in anti-Id antibodies: Possible application to vaccine production. Clin. Immunol. Immunopathol. 21, 397–403 (1981).

    Article  CAS  Google Scholar 

  28. Stein, K.E. Network regulation of the immune response to bacterial polysaccharide antigens. Curr. Top. Microbiol Immunol 119, 57–74 (1985).

    CAS  PubMed  Google Scholar 

  29. Kennedy, R.C., Dreesman, G.R. & Kohler, H. Vaccines utilizing internal image anti-idiotypic antibodies that mimic antigens of infectious organisms. BioTechniques 3, 404–409 (1985).

    Google Scholar 

  30. Su, S., Ward, M.M., Apicella, M.A. & Ward, R.E. A nontoxic, idiotope vaccine against gram-negative bacterial infections. J. Immunol 148, 234–238 (1992).

    CAS  PubMed  Google Scholar 

  31. Hawkins, R.E., Winter, G., Hamblin, T.J., Stevenson, F.K. & Russell, S.J. A genetic approach to idiotypic vaccination. J. Immunother. 14, 273–278 (1993).

    Article  CAS  Google Scholar 

  32. Eldridge, J., Hammond, C., Meulbroek, J., Gilley, R. & Tice, T. Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the Peyer's patches. J. Controlled Release 11, 205–214 (1990).

    Article  CAS  Google Scholar 

  33. Challacombe, S., Rahman, D., Jeffery, H., Davis, S. & ÓHagan, D. Enhanced secretory IgA and systemic IgG antibody responses after oral immunization with biodegradable microparticles containing antigen. Immunology 76, 164–168 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Marx, P.A. et al. Protection against vaginal SIV transmission with microencap-sulated vaccine. Science 260, 1323–1327 (1993).

    Article  CAS  Google Scholar 

  35. Whittum-Hudson, J.A., ÓBrien, T.P. & Prendergast, A. Murine model of ocular infection by a human biovar of Chlamydia trachomatis. Invest. Ophthalmol Vis. Sci. 36, 1976–1987 (1995).

    CAS  PubMed  Google Scholar 

  36. Blanchard, T.G., An, L., Troidle, K.M., Tirrell, S.M. & MacDonald, A.B. Internal image of exoglycolipid genus-specific antigen produced by anti-idiotype. in Chlamydial Infections (eds. Bowie, W.R. et al) 205–208 (Cambridge Univ. Press, Cambridge, 1990).

    Google Scholar 

  37. Troidle, K.M. Characterization of a genus-specific chlamydial antigen. Ph.D. thesis, Univ. Massachusetts, Amherst. (University Microfilms, Ann Arbor, Michigan, 1992).

    Google Scholar 

  38. Scieux, C. et al. Evaluation of a new chemiluminometric immunoassay, Magic Lite Chlamydia, for detecting Chlamydia trachomatis antigen from urogenital specimens. Sex. Transm. Dis. 19, 161–164 (1992).

    Article  CAS  Google Scholar 

  39. Murdin, A.D., Su, H., Klein, M.H. & Caldwell, H.D. Poliovirus hybrids expressing neutralization epitopes from variable domains I and IV of the major outer membrane protein of Chlamydia trachomatis elicit broadly cross-reactive C. tra-dwmfltfs-neutralizing antibodies. Infect. Immun. 63, 1116–1121 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 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 antibodies do not protect against chlamydial genital tract infection. Vaccine 13, 1023–1032 (1995).

    Article  CAS  Google Scholar 

  41. Brossay, L. et al. Mimicry of a neutralizing epitope of the major outer membrane protein of Chlamydia trachomatis by anti-idiotypic antibodies. Infect. Immun. 62, 341–347 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Jerne, N.K. Towards a network theory of the immune system. Ann. Immunol (Inst Pasteur) 125C, 373–389 (1974).

    CAS  Google Scholar 

  43. Fields, B.A., Goldbaum, F.A., Ysern, X., Poljak, R.J. & Mariuzza, R.A. Molecular basis of antigen mimicry by an anti-idiotope. Nature 374, 739–742 (1995).

    Article  CAS  Google Scholar 

  44. Westerink, M.A. & Apicella, M.A. Anti-idiotypic antibodies as vaccines against carbohydrate antigens [Review]. Springer Semin. Immunopathol 15, 227–234 (1993).

    Article  CAS  Google Scholar 

  45. Rees, A.D.M. et al. T cell activation by anti-idiotypic antibody: Mechanism of interaction with antigen-reactive T cell. Eur. J. Immunol. 17, 197–201 (1987).

    Article  CAS  Google Scholar 

  46. Taylor, H.R., Johnson, S.L., Schachter, J., Caldwell, H.D. & Prendergast, R.A. Pathogenesis of trachoma: The stimulus for inflammation. J. Immunol. 138, 3023–3027 (1987).

    CAS  PubMed  Google Scholar 

  47. Kiyono, H. & McGhee, J.R. T helper cells for mucosal immune responses. in Handbook of Mucosal Immunology. (ed. Ogra, P.L.) 263–274 (Academic Press, New York, 1994).

    Chapter  Google Scholar 

  48. Igietseme, J.U. et al. Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone. Reg. Immunol. 5, 317–324 (1993).

    CAS  PubMed  Google Scholar 

  49. Magee, D.M. et al. Role of CD8 T cells in primary chlamydia infection. Infect. Immun. 63, 516–521 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Harlow, E. & Lane, D. The Antibodies, 139–243 (Cold Spring Harbor Press, Cold Spring Harbor, New York, 1994).

    Google Scholar 

  51. Cohen, S., Yoshioka, T., Lucarelli, M., Hwang, L. & Langer, R. Controlled delivery systems for proteins based on poly (lactic/glycolic acid) microspheres. Pharm. Res. 8, 713–720 (1991).

    Article  CAS  Google Scholar 

  52. Salehi-Had, S. & Saltzman, W.M. Controlled intracranial delivery of antibodies in the rat. in Protein Formulations and Delivery. (eds. Cleland, J. & Langer, R.) 278–298 [(ACS (Am. Chem. Soc.) Symp. Series, Washington, DC, 1994)].

    Chapter  Google Scholar 

  53. Taylor, H.R., Agarwala, N. & Johnson, S.L. Detection of experimental Chlamydia trachomatis eye infection in conjunctival smears and in tissue culture by use of fluorescein-conjugated monoclonal antibody. J. Clin. Microbiol 20, 391–395 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Byrne, G.I. et al. Workshop on in vitro neutralization of Chlamydia trachomatis: Summary of proceedings. J. Infect. Dis. 168, 415–420 (1993).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Judith A. Whittum-Hudson & Ling-Ling An

    Present address: Department of Neuropharmacology, Scripps Research Institute, 10666 North Toney Pines Road, La folia, California, 92034, USA

  2. W. Mark Saltzman

    Present address: School of Chemical Engineering, Cornell University, Campus Road, Ithaca, New York, 14853, USA

Authors and Affiliations

  1. The Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287-9142

    Judith A. Whittum-Hudson & Robert A. Prendergast

  2. Department of Microbiology, University of Massachusetts, North Pleasant Street, Amherst, Massachusetts, 01003, USA

    Ling-Ling An & A. Bruce Macdonald

  3. Department of Chemical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland, 21218, USA

    W. Mark Saltzman

Authors
  1. Judith A. Whittum-Hudson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling-Ling An
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Mark Saltzman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert A. Prendergast
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Bruce Macdonald
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Whittum-Hudson, J., An, LL., Saltzman, W. et al. Oral immunization with an anti–idiotypic antibody to the exoglycolipid antigen protects against experimental Chlamydia trachomatis infection. Nat Med 2, 1116–1121 (1996). https://doi.org/10.1038/nm1096-1116

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1096-1116

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing