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. 1997 Nov;65(11):4661–4667. doi: 10.1128/iai.65.11.4661-4667.1997

Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice.

L K Bockenstedt 1, E Hodzic 1, S Feng 1, K W Bourrel 1, A de Silva 1, R R Montgomery 1, E Fikrig 1, J D Radolf 1, S W Barthold 1
PMCID: PMC175668  PMID: 9353047

Abstract

Antibodies to the outer surface proteins (Osps) A, B, and C of the spirochete Borrelia burgdorferi can prevent infection in animal models of Lyme borreliosis. We have previously demonstrated that immune serum from mice infected with B. burgdorferi N40 can also prevent challenge infection and induce disease regression in infected mice. The antigens targeted by protective and disease-modulating antibodies are presently unknown, but they do not include Osp A or Osp B. Because Osp C antibodies are present in immune mouse serum, we investigated the ability of hyperimmune serum to recombinant Osp C (N40) to protect mice against challenge infection with N40 spirochetes. In both active and passive immunization studies, Osp C (N40) antiserum failed to protect mice from challenge infection with cultured organisms. Mice actively immunized with recombinant Osp C (N40) were susceptible to tick-borne challenge infection, and nymphal ticks remained infected after feeding on Osp C-hyperimmunized mice. In contrast, similar immunization studies performed with Osp C (PKo) antiserum prevented challenge infection of mice with a clone of PKo spirochetes pathogenic for mice. Both Osp C (N40) and Osp C (PKo) antisera showed minimal in vitro borreliacidal activity, and immunofluorescence studies localized Osp C beneath the outer membrane of both N40 and PKo spirochetes. We conclude that Osp C antibody-mediated immunity is strain specific and propose that differences in Osp C surface expression by spirochetes in vivo may account for strain-specific immunity.

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Selected References

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  1. Akins D. R., Porcella S. F., Popova T. G., Shevchenko D., Baker S. I., Li M., Norgard M. V., Radolf J. D. Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer surface protein F (OspF) homologue. Mol Microbiol. 1995 Nov;18(3):507–520. doi: 10.1111/j.1365-2958.1995.mmi_18030507.x. [DOI] [PubMed] [Google Scholar]
  2. Barbour A. G. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):521–525. [PMC free article] [PubMed] [Google Scholar]
  3. Barbour A. G., Tessier S. L., Todd W. J. Lyme disease spirochetes and ixodid tick spirochetes share a common surface antigenic determinant defined by a monoclonal antibody. Infect Immun. 1983 Aug;41(2):795–804. doi: 10.1128/iai.41.2.795-804.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barthold S. W., Bockenstedt L. K. Passive immunizing activity of sera from mice infected with Borrelia burgdorferi. Infect Immun. 1993 Nov;61(11):4696–4702. doi: 10.1128/iai.61.11.4696-4702.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barthold S. W., Feng S., Bockenstedt L. K., Fikrig E., Feen K. Protective and arthritis-resolving activity in sera of mice infected with Borrelia burgdorferi. Clin Infect Dis. 1997 Jul;25 (Suppl 1):S9–17. doi: 10.1086/516166. [DOI] [PubMed] [Google Scholar]
  6. Barthold S. W., Fikrig E., Bockenstedt L. K., Persing D. H. Circumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi. Infect Immun. 1995 Jun;63(6):2255–2261. doi: 10.1128/iai.63.6.2255-2261.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Barthold S. W., Sidman C. L., Smith A. L. Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. Am J Trop Med Hyg. 1992 Nov;47(5):605–613. doi: 10.4269/ajtmh.1992.47.605. [DOI] [PubMed] [Google Scholar]
  8. Bockenstedt L. K., Barthold S., Deponte K., Marcantonio N., Kantor F. S. Borrelia burgdorferi infection and immunity in mice deficient in the fifth component of complement. Infect Immun. 1993 May;61(5):2104–2107. doi: 10.1128/iai.61.5.2104-2107.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bockenstedt L. K., Fikrig E., Barthold S. W., Flavell R. A., Kantor F. S. Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice. J Immunol. 1996 Dec 15;157(12):5496–5502. [PubMed] [Google Scholar]
  10. Bockenstedt L. K., Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Inability of truncated recombinant Osp A proteins to elicit protective immunity to Borrelia burgdorferi in mice. J Immunol. 1993 Jul 15;151(2):900–906. [PubMed] [Google Scholar]
  11. Champion C. I., Blanco D. R., Skare J. T., Haake D. A., Giladi M., Foley D., Miller J. N., Lovett M. A. A 9.0-kilobase-pair circular plasmid of Borrelia burgdorferi encodes an exported protein: evidence for expression only during infection. Infect Immun. 1994 Jul;62(7):2653–2661. doi: 10.1128/iai.62.7.2653-2661.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cox D. L., Akins D. R., Bourell K. W., Lahdenne P., Norgard M. V., Radolf J. D. Limited surface exposure of Borrelia burgdorferi outer surface lipoproteins. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7973–7978. doi: 10.1073/pnas.93.15.7973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. De Silva A. M., Fikrig E. Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding. Am J Trop Med Hyg. 1995 Oct;53(4):397–404. doi: 10.4269/ajtmh.1995.53.397. [DOI] [PubMed] [Google Scholar]
  14. Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. doi: 10.1126/science.2237407. [DOI] [PubMed] [Google Scholar]
  15. Fikrig E., Barthold S. W., Sun W., Feng W., Telford S. R., 3rd, Flavell R. A. Borrelia burgdorferi P35 and P37 proteins, expressed in vivo, elicit protective immunity. Immunity. 1997 May;6(5):531–539. doi: 10.1016/s1074-7613(00)80341-6. [DOI] [PubMed] [Google Scholar]
  16. Fuchs R., Jauris S., Lottspeich F., Preac-Mursic V., Wilske B., Soutschek E. Molecular analysis and expression of a Borrelia burgdorferi gene encoding a 22 kDa protein (pC) in Escherichia coli. Mol Microbiol. 1992 Feb;6(4):503–509. doi: 10.1111/j.1365-2958.1992.tb01495.x. [DOI] [PubMed] [Google Scholar]
  17. Gilmore R. D., Jr, Kappel K. J., Dolan M. C., Burkot T. R., Johnson B. J. Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: evidence for a conformational protective epitope in OspC. Infect Immun. 1996 Jun;64(6):2234–2239. doi: 10.1128/iai.64.6.2234-2239.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ma Y., Seiler K. P., Tai K. F., Yang L., Woods M., Weis J. J. Outer surface lipoproteins of Borrelia burgdorferi stimulate nitric oxide production by the cytokine-inducible pathway. Infect Immun. 1994 Sep;62(9):3663–3671. doi: 10.1128/iai.62.9.3663-3671.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Montgomery R. R., Malawista S. E., Feen K. J., Bockenstedt L. K. Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease. J Exp Med. 1996 Jan 1;183(1):261–269. doi: 10.1084/jem.183.1.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morita M., Kawashima S., Ueno M., Kubota A., Iwasaki T. Effects of late reperfusion on infarct expansion and infarct healing in conscious rats. Am J Pathol. 1993 Aug;143(2):419–430. [PMC free article] [PubMed] [Google Scholar]
  21. Padula S. J., Sampieri A., Dias F., Szczepanski A., Ryan R. W. Molecular characterization and expression of p23 (OspC) from a North American strain of Borrelia burgdorferi. Infect Immun. 1993 Dec;61(12):5097–5105. doi: 10.1128/iai.61.12.5097-5105.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Preac-Mursic V., Wilske B., Patsouris E., Jauris S., Will G., Soutschek E., Rainhardt S., Lehnert G., Klockmann U., Mehraein P. Active immunization with pC protein of Borrelia burgdorferi protects gerbils against B. burgdorferi infection. Infection. 1992 Nov-Dec;20(6):342–349. doi: 10.1007/BF01710681. [DOI] [PubMed] [Google Scholar]
  23. Probert W. S., Crawford M., Cadiz R. B., LeFebvre R. B. Immunization with outer surface protein (Osp) A, but not OspC, provides cross-protection of mice challenged with North American isolates of Borrelia burgdorferi. J Infect Dis. 1997 Feb;175(2):400–405. doi: 10.1093/infdis/175.2.400. [DOI] [PubMed] [Google Scholar]
  24. Probert W. S., LeFebvre R. B. Protection of C3H/HeN mice from challenge with Borrelia burgdorferi through active immunization with OspA, OspB, or OspC, but not with OspD or the 83-kilodalton antigen. Infect Immun. 1994 May;62(5):1920–1926. doi: 10.1128/iai.62.5.1920-1926.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schaible U. E., Kramer M. D., Eichmann K., Modolell M., Museteanu C., Simon M. M. Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. Proc Natl Acad Sci U S A. 1990 May;87(10):3768–3772. doi: 10.1073/pnas.87.10.3768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schwan T. G., Piesman J., Golde W. T., Dolan M. C., Rosa P. A. Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909–2913. doi: 10.1073/pnas.92.7.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stevenson B., Bockenstedt L. K., Barthold S. W. Expression and gene sequence of outer surface protein C of Borrelia burgdorferi reisolated from chronically infected mice. Infect Immun. 1994 Aug;62(8):3568–3571. doi: 10.1128/iai.62.8.3568-3571.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Suk K., Das S., Sun W., Jwang B., Barthold S. W., Flavell R. A., Fikrig E. Borrelia burgdorferi genes selectively expressed in the infected host. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4269–4273. doi: 10.1073/pnas.92.10.4269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wilske B., Barbour A. G., Bergström S., Burman N., Restrepo B. I., Rosa P. A., Schwan T., Soutschek E., Wallich R. Antigenic variation and strain heterogeneity in Borrelia spp. Res Microbiol. 1992 Jul-Aug;143(6):583–596. doi: 10.1016/0923-2508(92)90116-6. [DOI] [PubMed] [Google Scholar]
  30. de Silva A. M., Telford S. R., 3rd, Brunet L. R., Barthold S. W., Fikrig E. Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. J Exp Med. 1996 Jan 1;183(1):271–275. doi: 10.1084/jem.183.1.271. [DOI] [PMC free article] [PubMed] [Google Scholar]

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