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Active immunization with pC protein ofBorrelia burgdorferi protects gerbils againstB. burgdorferi infection

Aktive Immunisierung mit pC-Protein von Borrelia burgdorferi hat bei Gerbils protektive Wirkung gegen die B. burgdorferi-Infektionen

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Summary

Serious infection due toBorrelia burgdorferi and the disseminated infection characteristic of the disease possess unique treatment problems. The wide and still increasing incidence of Lyme borreliosis as well as the problems in treatment call for effective prevention strategies by active immunization. Vaccination experiments were done to determine if active immunization of gerbils with recombinant OspA and pC protects against infection with strains ofB. burgdorferi. Gerbils were vaccinated with recombinant OspA and pC (20 kDa protein) and challenged four weeks later with a clone (derived fromB. burgdorferi strain PKo) which expresses an abundant amount of pC but only little OspA. Non-immunized gerbils challenged with the sameB. burgdorferi strain were used as controls. Both groups of immunized gerbils developed antibodies against the recombinant vaccines. The pC vaccinated group was protected against infection, whereas the OspA vaccinated group showed signs of infection. The non-vaccinated group developed generalised infection. These results show that pC should be considered as a further vaccine candidate and probably needs to be combined with OspA for an efficient vaccine againstB. burgdorferi.

Zusammenfassung

Weite Verbreitung und zunehmende Inzidenz der Lyme Borreliose sowie Therapieprobleme bei schweren Erkrankungsformen besonders im Spätstdadium der Infektion sind Gründe für die Entwicklung einer möglichen Alternative zur Antiobitikatherapie wie zum Beispiel Schutzimpfung. Die Schutzwirkung einer aktiven Immunisierung mit rekombinanten OspA und pC gegen die Infektion mitBorrelia burgdorferi wurde bei Gerbils geprüft. Die Tiere wurden mit rekombinanten OspA und pC vomB. burgdorferi-Stamm PKo immunisiert; die Infektion erfolgte vier Wochen nach der Immunisierung mit dem PKo-Stamm (schwache OspA, gute pC Expression). Als Kontrollgruppe dienten infizierte, nicht immunisierte Gerbils. Die immunisierten Tiere bildeten Antikörper gegen rekombinante Vakzine. Die mit pC immunisierten Tiere waren vor der Infektion geschützt, die Kontrollgruppe zeigte eine generalisierte Infektion. Die Immunisierung mit OspA schützte nicht, die Tiere zeigten, wie die Kontrollgruppe Merkmale der Infektion. Die Ergebnisse dieser Studie zeigen, daß pC für eine Immunisierung in Frage kommt. Eine Kombination von OspA und pC scheint für eine effektive Vakzine gegenBorrelia burgdorferi nötig zu sein.

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References

  1. Burgdorfer, W., Barbour, A. G., Hayes, S. F., Benach, J. L., Grunwald, E., Davis, J. P. Lyme disease — a tick-borne spirochetosis? Science 216 (1982) 1317–1319.

    Article  CAS  PubMed  Google Scholar 

  2. Steere, A. C. Medical progress — Lyme disease. N. Engl. J. Med. 321 (1989) 586–596.

    Article  CAS  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. 152 (1985) 478–484.

    Article  CAS  PubMed  Google Scholar 

  4. Wilske, B., Anderson, J. F., Baranton, G., Barbour, A. G., Hovind-Hougen, K., Johnson, R. C., Preac-Mursic, V. Taxonomy ofBorrelia spp. Scand. J. Infect. Dis. (Suppl. 77) (1991) 108–129.

    Google Scholar 

  5. Jonsson, M., Noppa, L., Barbour, A. G., Bergström, S. Heterogeneity of osp operons of three isolates of different geographic origins. Infect. Immun. 60 (1992) 1845–1853.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Babour, A. G. Antigenic variations of surface proteins ofBorrelia species. Rev. Infect. Dis. 10 (1988) 399–402.

    Article  Google Scholar 

  7. Wilske, B., Preac-Mursic, V., Schierz, G., Kühbeck, R., Barbour, A. G., Kramer, M. Antigenic variability ofBorrelia burgdorferi. Ann. N. Y. Acad. Sci. 539 (1988) 126–143.

    Article  CAS  PubMed  Google Scholar 

  8. Bundoc, V. G., Barbour, A. Clonal polymorphisms of outer membrane protein OspB ofBorrelia burgdorferi. Infect. Immun. 57 (1989) 2733–2741.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Postic, D., Edlinger, C., Richaud, C., Grimont, F., Dufresne, Y., Perolat, P., Baranton, G., Grimont, P. A. D. Two genomic species inBorrelia burgdorferi. Res. Microbiol. 141 (1990) 465–475.

    Article  CAS  PubMed  Google Scholar 

  10. Adam, T., Gassmann, G. S., Rasiah, C., Göbel, U. B. Phenotypic and genotypic analysis ofBorrelia burgdorferi isolates from various sources. Infect. Immun. 59 (1991) 2579–2585.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Baranton, G., Postic, D., Saint Girons, I., Boerlin, P., Piffaretti, J.-C., Assous, M., Grimont, P. A. D.: Delineation ofBorrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Intern. J. System Bacteriol. 42 (1992) in press.

  12. Marconi, R. T., Lubke, L., Hauglum, W., Garon, C. F. Species-specific identification of and distinction betweenBorrelia burgdorferi genomic groups by using 16S rRNA-directed oligonucleotide probes. J. Clin. Microbiol. 30 (1992) 628–632.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Johnson, R. C., Kodner, C., Russel, M., Duray, P. Experimental infection of the hamster withB. burgdorferi. Ann. N. Y. Acad. Sci. 539 (1988) 258–263.

    Article  CAS  PubMed  Google Scholar 

  14. Barthold, S. W., Moody, K. D., Terwilliger, G. A., Duray, P. H., Jacoby, R. O., Steere, A. C. Experimental Lyme arthritis in rats infected withBorrelia burgdorferi. Infect. Dis. 157 (1988) 842–846.

    Article  CAS  Google Scholar 

  15. Preac-Mursic, V., Patsouris, E., Wilske, B., Reinhardt, S., Groß, B., Mehraein, P. Persistence ofBorrelia burgdorferi and histopathological alterations in experimentally infected animals; comparison with histopathological findings in human Lyme disease. Infection 18 (1990) 332–341.

    Article  CAS  PubMed  Google Scholar 

  16. 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. 170 (1989) 1427–1432.

    Article  CAS  PubMed  Google Scholar 

  17. Johnson, R. C., Kodner, C., Russell, M. Passive immunisation of hamsters against experimental infection with the Lyme disease spirochete. Infect. Immun. 53 (1986) 713–714.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Johnson, R. C., Kodner, C., Russel, M. Active immunization of hamsters against experimental infection withBorrelia burgdorferi. Infect. Immun. 54 (1986) 897–898.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 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 250 (1990) 553–556.

    Article  CAS  PubMed  Google Scholar 

  20. Simon, M. M., Schaible, U. E., Kramer, M. D., Eckerskorn, C., Müller-Hermelink, H. K., Wallich, R. Recombinant outer surface protein A fromBorrelia burgdorferi induces antibodies protective against spirochetal infection in mice. J. Infect. Dis. 164 (1991) 123–132.

    Article  CAS  PubMed  Google Scholar 

  21. Schaible, U. E., Kramer, M. D., Eichmann, K., Modolell, M., Museteanu, C., Simon, M. M. Monoclonal antibodies specific for the outer surface protein (OspA) prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. Proc. Natl. Acad. Sci. USA 87 (1990) 3768–3772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zumstein, G., Fuchs, R., Hofmann, A., Preac-Mursic, V., Soutschek, E., Wilske, B. Genetic polymorphism of the gene encoding the outer surface protein A (OspA) ofBorrelia burgdorferi. Med. Microbiol. Immunol. 181 (1992) 57–70.

    Article  CAS  PubMed  Google Scholar 

  23. Barbour, A. G., Burgdorfer, W., Grunwald, E., Steere, A. C. Antibodies of patients with Lyme disease to components of theIxodes dammini spirochete. J. Clin. Invest. 72 (1983) 504–515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wilske, B., Preac-Mursic, V., Fuchs, R., Bruckbauer, H., Hofmann, A., Zumstein, G., Jauris, S., Soutschek, E., Motz, M. Immunodominant proteins ofBorrelia burgdorferi; implications for improving serodiagnosis of Lyme borreliosis. In:Neu, H. C. (ed.): New antibacterial strategies. Churchill Livingstone, London 1990, pp. 47–63.

    Google Scholar 

  25. Wilske, B., Preac-Mursic, V., Schierz, G., Liegl, G., Gueye, W. Detection of IgM- and IgG antibodies toBorrelia burgdorferi using different strains as antigen. Proceedings of the Lyme borreliosis update Europe. Baden 2.–4. Juni 1987. Zbl. Bakt. Suppl. 18 (1989) 299–309.

    Google Scholar 

  26. Bissett, M. L., Hill, W. Characterization ofBorrelia burgdorferi strains isolated fromIxodes pacificus ticks in California. J. Clin. Microbiol. 25 (1987) 2296–2301.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Fuchs, R., Jauris, S., Lottspeich, F., Preac-Mursic, V., Wilske, B., Soutschek, E. Molecular analysis and expression of aBorrelia burgdorferi gene encoding a 22 kDa protein (pC) inEscherichia coli. Mol. Microbiol. 6 (1992) 503–509.

    Article  CAS  PubMed  Google Scholar 

  28. Preac-Mursic, V., Wilske, B., Reinhardt, S. Culture ofBorrelia burgdorferi on six solid media. Eur. J. Microbiol. Infect. Dis. 10 (1991) 1076–1079.

    Article  CAS  Google Scholar 

  29. Preac-Mursic, V., Wilske, B., Schierz, G. EuropeanBorrelia burgdorferi isolated from humans and ticks: culture conditions and antibiotic susceptibility. Zbl. Bakt. Hyg. A 263 (1986) 112–118.

    Google Scholar 

  30. Preac-Mursic, V., Wilske, B., Schierz, G., Holnburger, M., Süß, E. In vitro andin vivo susceptibility ofBorrelia burgdorferi. Eur. J. Clin. Microbiol. 6 (1987) 424–426.

    Article  Google Scholar 

  31. Wilske, B., Fuchs, R., Jauris, S., Preac-Mursic, V., Soutschek, E., Zumstein, G.: Recombinant antigens for antibody detection in Lyme borreliosis. In 5 ECCMID Oslo (1991).

  32. Preac-Mursic, V., Wilske, B., Schierz, G., Süß, E., Gross, B. Comparative antimicrobial activity of the new macrolides againstBorrelia burgdorferi. Eur. J. Clin. Microbiol. Infect. Dis. 8 (1989) 651–653.

    Article  CAS  PubMed  Google Scholar 

  33. 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. Immun. 148 (1992) 2256–2260.

    CAS  PubMed  Google Scholar 

  34. Duray, P. H., Steere, A. C. The spectrum of organ and systems pathology in human Lyme disease. Zbl. Bakt. Hyg. A 263 (1986) 169–178.

    Google Scholar 

  35. Mac Donald, A. Lyme disease: a neuro-ophtalmologic view. J. Clin. Neuro. Ophtalmol. 7 (1987) 185–190.

    CAS  Google Scholar 

  36. Lampert, F. Infantile multisystem inflammatory disease. Another case of a new syndrome. Eur. J. Pediatr. 444 (1984) 593–596.

    Google Scholar 

  37. Steere, A. C., Duray, P. H., Kaufman, G., Wormser, P. Unilateral blindness caused by infection with the Lyme disease spirochete,Borrelia burgdorferi. Ann. Intern. Med. 103 (1985) 382–384.

    Article  CAS  PubMed  Google Scholar 

  38. Camponovo, F., Meier, C. Neuropathy of vasculitis origin in a case of Garin-Bujadoux-Bannwarth syndrome with positiveBorrelia antibody response. J. Neurol. 233 (1986) 69–72.

    Article  CAS  PubMed  Google Scholar 

  39. Vallat, J. M., Hugon, J., Lubeau, M., Leboutet, M. J., Dumas, M., Deproges-Gotteron, M. Tick-bite meningoradiculoneuritis: clinical, electrophysiologic and histologic findings in ten cases. Neurology 37 (1987) 749–753.

    Article  CAS  PubMed  Google Scholar 

  40. Rothemund, E., Patsouris, E., Feiden, W., Pfister, W., Mehraein, S. Polyneuropathy in Lyme borreliosis: histopathological findings in sural nerve. Biopsy and experimental data. Clin. Neuropathol. 8 (1989) 247.

    Google Scholar 

  41. Chavanet, P., Pillon, D., Lancon, J. P., Waldner-Combernoux, A., Maringe, E., Portier, H. Granulomatous hepatitis associated with Lyme disease. Lancet ii (1987) 523–524.

    Google Scholar 

  42. Reimers, C. D., Pongratz, D. E., Neubert, U., Pilz, A., Hübner, G., Naegele, M., Wilske, B., Duray, P. H., de Koning, J. C. Myositis caused byB. burgdorferi: report of four cases. J. Neurol. Sci. 91 (1989) 215–226.

    Article  CAS  PubMed  Google Scholar 

  43. Abele, D. C., Anders, K. H., Chandler, F. W. Benign lymphocytic infiltration (Jessner-Kauot), another manifestation of borreliosis. J. Am. Acad. Dermatol. 21 (1989) 795–797.

    Article  CAS  PubMed  Google Scholar 

  44. Berger, B. W., Kaplan, M. H., Rothenberg, I. R., Barbour, A. G. Isolation and characterization of the Lyme disease spirochete from the skin of patients with erythema chronicum migrans. J. Am. Acad. Dermatol. 13 (1985) 444–449.

    Article  CAS  PubMed  Google Scholar 

  45. Duray, P. H. The surgical pathology of human Lyme disease: an enlarging picture. Am. J. Surg. Pathol. II (Suppl. 1) (1987) 47–60.

    Article  Google Scholar 

  46. Pachner, A. R., Duray, P., Steere, A. C. Central nervous system manifestations of Lyme disease. Arch. Neurol. 46 (1989) 790–795.

    Article  CAS  PubMed  Google Scholar 

  47. Steere, A. C., Malawista, S. E., Hardin, J. A., Ruddy, S., Askenase, P. W., Andiman, W. A. Erythema chronicum migrans and Lyme arthritis: the enlarging clinical spectrum. Ann. Intern. Med. 86 (1977) 685–698.

    Article  CAS  PubMed  Google Scholar 

  48. Johnston, Y. E., Duray, P. H., Steere, A. C., Kashgarin, M., Buza, J., Malawista, S. E., Askenase, P. W. Lyme arthritis spirochetes found in synovial microangiopathic lesions. A. J. P. 118 (1985) 26–34.

    CAS  Google Scholar 

  49. Duray, P. H., Johnson, R. C. The histopathology of experimentally infected hamsters with the Lyme disease spirochete,Borrelia burgdorferi. (42251) Proc. Soc. Exp. Biol. Med. 181 (1986) 263–269.

    Article  CAS  Google Scholar 

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Preac-Mursic, V., Wilske, B., Jauris, S. et al. Active immunization with pC protein ofBorrelia burgdorferi protects gerbils againstB. burgdorferi infection. Infection 20, 342–349 (1992). https://doi.org/10.1007/BF01710681

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