Skip to main content
PMC home page
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
. 1990 May;87(10):3768–3772. doi: 10.1073/pnas.87.10.3768

Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice.

U E Schaible 1, M D Kramer 1, K Eichmann 1, M Modolell 1, C Museteanu 1, M M Simon 1
PMCID: PMC53984  PMID: 2339119

Abstract

We have recently shown that viable Borrelia burgdorferi organisms induce a chronic infection associated with arthritis and carditis in severe combined immunodeficiency (scid) mice but not in immunocompetent mice. The disease is similar to that found in patients suffering from Lyme disease. We now show that B. burgdorferi-specific immune mouse sera as well as a monoclonal antibody to the spirochetal outer surface antigen A (31 kDa) but not monoclonal antibodies specific for the 41-kDa antigenic component of the periplasmic flagella are able to prevent (or mitigate) the development of the disease in scid mice when passively transferred at the time of the bacterial inoculation. The identification of a B. burgdorferi-associated protective antigen suggests that the corresponding spirochetal protein should be tested as a vaccine against Lyme disease.

Full text

PDF
3768

Images in this article

3770Image
on p.3770
3771Image
on p.3771
3771Image
on p.3771
3771Image
on p.3771
3771Image
on p.3771

Selected References

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

  1. Barbour A. G., Burgdorfer W., Grunwaldt E., Steere A. C. Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete. J Clin Invest. 1983 Aug;72(2):504–515. doi: 10.1172/JCI110998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbour A. G., Hayes S. F., Heiland R. A., Schrumpf M. E., Tessier S. L. A Borrelia-specific monoclonal antibody binds to a flagellar epitope. Infect Immun. 1986 May;52(2):549–554. doi: 10.1128/iai.52.2.549-554.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbour A. G., Heiland R. A., Howe T. R. Heterogeneity of major proteins in Lyme disease borreliae: a molecular analysis of North American and European isolates. J Infect Dis. 1985 Sep;152(3):478–484. doi: 10.1093/infdis/152.3.478. [DOI] [PubMed] [Google Scholar]
  4. Barthold S. W., Moody K. D., Terwilliger G. A., Duray P. H., Jacoby R. O., Steere A. C. Experimental Lyme arthritis in rats infected with Borrelia burgdorferi. J Infect Dis. 1988 Apr;157(4):842–846. doi: 10.1093/infdis/157.4.842. [DOI] [PubMed] [Google Scholar]
  5. Benach J. L., Coleman J. L., Garcia-Monco J. C., Deponte P. C. Biological activity of Borrelia burgdorferi antigens. Ann N Y Acad Sci. 1988;539:115–125. doi: 10.1111/j.1749-6632.1988.tb31845.x. [DOI] [PubMed] [Google Scholar]
  6. Benach J. L., Fleit H. B., Habicht G. S., Coleman J. L., Bosler E. M., Lane B. P. Interactions of phagocytes with the Lyme disease spirochete: role of the Fc receptor. J Infect Dis. 1984 Oct;150(4):497–507. doi: 10.1093/infdis/150.4.497. [DOI] [PubMed] [Google Scholar]
  7. Bergström S., Bundoc V. G., Barbour A. G. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol Microbiol. 1989 Apr;3(4):479–486. doi: 10.1111/j.1365-2958.1989.tb00194.x. [DOI] [PubMed] [Google Scholar]
  8. Coe J., Peel L., Smith R. F. Biologic activities of peromyscus 7S-gamma-1 and 7S-gamma-2 globulins. J Immunol. 1970 Oct;105(4):1006–1010. [PubMed] [Google Scholar]
  9. Craft J. E., Fischer D. K., Shimamoto G. T., Steere A. C. Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new immunoglobulin M response and expansion of the immunoglobulin G response late in the illness. J Clin Invest. 1986 Oct;78(4):934–939. doi: 10.1172/JCI112683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dattwyler R. J., Volkman D. J., Halperin J. J., Luft B. J., Thomas J., Golightly M. G. Specific immune responses in Lyme borreliosis. Characterization of T cell and B cell responses to Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:93–102. doi: 10.1111/j.1749-6632.1988.tb31842.x. [DOI] [PubMed] [Google Scholar]
  11. Deschryver-Kecskemeti K., Bancroft G. J., Bosma G. C., Bosma M. J., Unanue E. R. Pathology of Listeria infection in murine severe combined immunodeficiency. A study by immunohistochemistry and electron microscopy. Lab Invest. 1988 Jun;58(6):698–705. [PubMed] [Google Scholar]
  12. Hejka A., Schmitz J. L., England D. M., Callister S. M., Schell R. F. Histopathology of Lyme arthritis in LSH hamsters. Am J Pathol. 1989 May;134(5):1113–1123. [PMC free article] [PubMed] [Google Scholar]
  13. Johnson R. C., Kodner C., Russell M., Duray P. H. Experimental infection of the hamster with Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:258–263. doi: 10.1111/j.1749-6632.1988.tb31859.x. [DOI] [PubMed] [Google Scholar]
  14. Johnson R. C., Kodner C., Russell M. Passive immunization of hamsters against experimental infection with the Lyme disease spirochete. Infect Immun. 1986 Sep;53(3):713–714. doi: 10.1128/iai.53.3.713-714.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kochi S. K., Johnson R. C. Role of immunoglobulin G in killing of Borrelia burgdorferi by the classical complement pathway. Infect Immun. 1988 Feb;56(2):314–321. doi: 10.1128/iai.56.2.314-321.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Munder P. G., Modolell M., Hoelzl Wallach D. F. Cell propagation on films of polymeric fluorocarbon as a means to regulate pericellular pH and pO(2) in cultured monolayers. FEBS Lett. 1971 Jun 24;15(3):191–196. doi: 10.1016/0014-5793(71)80309-5. [DOI] [PubMed] [Google Scholar]
  17. Schaible U. E., Kramer M. D., Museteanu C., Zimmer G., Mossmann H., Simon M. M. The severe combined immunodeficiency (scid) mouse. A laboratory model for the analysis of Lyme arthritis and carditis. J Exp Med. 1989 Oct 1;170(4):1427–1432. doi: 10.1084/jem.170.4.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schmitz J. L., Schell R. F., Hejka A. G., England D. M. Passive immunization prevents induction of Lyme arthritis in LSH hamsters. Infect Immun. 1990 Jan;58(1):144–148. doi: 10.1128/iai.58.1.144-148.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schmitz J. L., Schell R. F., Hejka A., England D. M., Konick L. Induction of lyme arthritis in LSH hamsters. Infect Immun. 1988 Sep;56(9):2336–2342. doi: 10.1128/iai.56.9.2336-2342.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Steere A. C., Grodzicki R. L., Kornblatt A. N., Craft J. E., Barbour A. G., Burgdorfer W., Schmid G. P., Johnson E., Malawista S. E. The spirochetal etiology of Lyme disease. N Engl J Med. 1983 Mar 31;308(13):733–740. doi: 10.1056/NEJM198303313081301. [DOI] [PubMed] [Google Scholar]
  21. Wallich R., Schaible U. E., Simon M. M., Heiberger A., Kramer M. D. Cloning and sequencing of the gene encoding the outer surface protein A (OspA) of a European Borrelia burgdorferi isolate. Nucleic Acids Res. 1989 Nov 11;17(21):8864–8864. doi: 10.1093/nar/17.21.8864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wilske B., Preac-Mursic V., Schierz G., Kühbeck R., Barbour A. G., Kramer M. Antigenic variability of Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:126–143. doi: 10.1111/j.1749-6632.1988.tb31846.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES