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. 1995 May;63(5):1658–1662. doi: 10.1128/iai.63.5.1658-1662.1995

Selection of variant Borrelia burgdorferi isolates from mice immunized with outer surface protein A or B.

E Fikrig 1, H Tao 1, S W Barthold 1, R A Flavell 1
PMCID: PMC173206  PMID: 7729870

Abstract

A nonclonal population of Borrelia burgdorferi N40 (passage 3) that survived protective immunity following challenge inoculation of outer surface protein (Osp) A- or B-hyperimmunized mice were characterized for the molecular basis of evasion of immunity. Two of six B. burgdorferi isolates, cultured from OspA-immunized mice, had antigenic diversity in the carboxyl terminus of OspA and did not bind to the protective OspA monoclonal antibody designated IXDII. However, OspA-immunized mice challenged with these variants were fully protected. Moreover, B. burgdorferi isolates with a point mutation in ospB, which results in a truncated OspB that does not bind to protective OspB monoclonal antibody 7E6C, were frequently enriched after infection of OspB-immunized mice. These studies suggest that the incomplete efficacy of an OspA- or OspB-based vaccine may be partly due to immunomediated in vivo selective pressure, resulting in the persistence of some spirochetes that do not bind to protective antibodies.

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Selected References

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  1. Coleman J. L., Rogers R. C., Benach J. L. Selection of an escape variant of Borrelia burgdorferi by use of bactericidal monoclonal antibodies to OspB. Infect Immun. 1992 Aug;60(8):3098–3104. doi: 10.1128/iai.60.8.3098-3104.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Erdile L. F., Brandt M. A., Warakomski D. J., Westrack G. J., Sadziene A., Barbour A. G., Mays J. P. Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA. Infect Immun. 1993 Jan;61(1):81–90. doi: 10.1128/iai.61.1.81-90.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Fikrig E., Barthold S. W., Persing D. H., Sun X., Kantor F. S., Flavell R. A. Borrelia burgdorferi strain 25015: characterization of outer surface protein A and vaccination against infection. J Immunol. 1992 Apr 1;148(7):2256–2260. [PubMed] [Google Scholar]
  5. Fikrig E., Tao H., Kantor F. S., Barthold S. W., Flavell R. A. Evasion of protective immunity by Borrelia burgdorferi by truncation of outer surface protein B. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4092–4096. doi: 10.1073/pnas.90.9.4092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fikrig E., Telford S. R., 3rd, Barthold S. W., Kantor F. S., Spielman A., Flavell R. A. Elimination of Borrelia burgdorferi from vector ticks feeding on OspA-immunized mice. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5418–5421. doi: 10.1073/pnas.89.12.5418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fikrig E., Telford S. R., 3rd, Wallich R., Chen M., Lobet Y., Matuschka F. R., Kimsey R. B., Kantor F. S., Barthold S. W., Spielman A. Vaccination against Lyme disease caused by diverse Borrelia burgdorferi. J Exp Med. 1995 Jan 1;181(1):215–221. doi: 10.1084/jem.181.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. France L. L., Kieleczawa J., Dunn J. J., Luft B. J., Hind G., Sutherland J. C. Evidence for an alpha-helical epitope on outer surface protein A from the Lyme disease spirochete, Borrelia burgdorferi: an application of steady-state and time-resolved fluorescence quenching techniques. Biochim Biophys Acta. 1993 Oct 6;1202(2):287–296. doi: 10.1016/0167-4838(93)90018-m. [DOI] [PubMed] [Google Scholar]
  9. Johnson R. C., Kodner C., Russell M. Active immunization of hamsters against experimental infection with Borrelia burgdorferi. Infect Immun. 1986 Dec;54(3):897–898. doi: 10.1128/iai.54.3.897-898.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Lovrich S. D., Callister S. M., Lim L. C., Schell R. F. Seroprotective groups among isolates of Borrelia burgdorferi. Infect Immun. 1993 Oct;61(10):4367–4374. doi: 10.1128/iai.61.10.4367-4374.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Persing D. H., Mathiesen D., Podzorski D., Barthold S. W. Genetic stability of Borrelia burgdorferi recovered from chronically infected immunocompetent mice. Infect Immun. 1994 Aug;62(8):3521–3527. doi: 10.1128/iai.62.8.3521-3527.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Rosa P. A., Schwan T., Hogan D. Recombination between genes encoding major outer surface proteins A and B of Borrelia burgdorferi. Mol Microbiol. 1992 Oct;6(20):3031–3040. doi: 10.1111/j.1365-2958.1992.tb01761.x. [DOI] [PubMed] [Google Scholar]
  15. Sadziene A., Barbour A. G., Rosa P. A., Thomas D. D. An OspB mutant of Borrelia burgdorferi has reduced invasiveness in vitro and reduced infectivity in vivo. Infect Immun. 1993 Sep;61(9):3590–3596. doi: 10.1128/iai.61.9.3590-3596.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Schaible U. E., Wallich R., Kramer M. D., Gern L., Anderson J. F., Museteanu C., Simon M. M. Immune sera to individual Borrelia burgdorferi isolates or recombinant OspA thereof protect SCID mice against infection with homologous strains but only partially or not at all against those of different OspA/OspB genotype. Vaccine. 1993;11(10):1049–1054. doi: 10.1016/0264-410x(93)90132-h. [DOI] [PubMed] [Google Scholar]
  19. Schutzer S. E., Coyle P. K., Dunn J. J., Luft B. J., Brunner M. Early and specific antibody response to OspA in Lyme Disease. J Clin Invest. 1994 Jul;94(1):454–457. doi: 10.1172/JCI117346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sears J. E., Fikrig E., Nakagawa T. Y., Deponte K., Marcantonio N., Kantor F. S., Flavell R. A. Molecular mapping of Osp-A mediated immunity against Borrelia burgdorferi, the agent of Lyme disease. J Immunol. 1991 Sep 15;147(6):1995–2000. [PubMed] [Google Scholar]
  21. Simon M. M., Schaible U. E., Kramer M. D., Eckerskorn C., Museteanu C., Müller-Hermelink H. K., Wallich R. Recombinant outer surface protein a from Borrelia burgdorferi induces antibodies protective against spirochetal infection in mice. J Infect Dis. 1991 Jul;164(1):123–132. doi: 10.1093/infdis/164.1.123. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Stover C. K., Bansal G. P., Hanson M. S., Burlein J. E., Palaszynski S. R., Young J. F., Koenig S., Young D. B., Sadziene A., Barbour A. G. Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine. J Exp Med. 1993 Jul 1;178(1):197–209. doi: 10.1084/jem.178.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sădziene A., Rosa P. A., Thompson P. A., Hogan D. M., Barbour A. G. Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization. J Exp Med. 1992 Sep 1;176(3):799–809. doi: 10.1084/jem.176.3.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Telford S. R., 3rd, Fikrig E., Barthold S. W., Brunet L. R., Spielman A., Flavell R. A. Protection against antigenically variable Borrelia burgdorferi conferred by recombinant vaccines. J Exp Med. 1993 Aug 1;178(2):755–758. doi: 10.1084/jem.178.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wienecke R., Neubert U., Volkenandt M. Cross immunity among types of Borrelia burgdorferi. Lancet. 1993 Aug 14;342(8868):435–435. doi: 10.1016/0140-6736(93)92848-n. [DOI] [PubMed] [Google Scholar]

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