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Infect Immun. 1994 July; 62(7): 2825–2833.
PMCID: PMC302888

Development of destructive arthritis in vaccinated hamsters challenged with Borrelia burgdorferi.


We present the first direct evidence that adverse effects, particularly severe destructive arthritis, can develop in vaccinated hamsters after challenge with Borrelia burgdorferi sensu lato isolates. Hamsters were vaccinated with a whole-cell preparation of Formalin-inactivated B. burgdorferi sensu stricto isolate C-1-11 in adjuvant. A severe destructive arthritis was readily evoked in vaccinated hamsters challenged with the homologous B. burgdorferi sensu stricto isolate C-1-11 before high levels of protective borreliacidal antibody developed. Once high levels of C-1-11 borreliacidal antibody developed, hamsters were protected from homologous challenge and development of arthritis. Vaccinated hamsters, however, still developed severe destructive arthritis when challenged with other isolates of the three genomic groups of B. burgdorferi sensu lato (B. burgdorferi sensu stricto isolate 297, Borrelia garinii isolate LV4, and Borrelia afzelii isolate BV1) despite high levels of C-1-11 specific borreliacidal antibody. Vaccines that contained whole spirochetes in adjuvant induced destructive arthritis, but this effect was not dependent on the isolate of B. burgdorferi sensu lato or the type of adjuvant. These studies demonstrate that caution is necessary when employing whole spirochetes in adjuvant for vaccination to prevent Lyme borreliosis. Additional studies are needed to identify the antigen(s) responsible for the induction and activation of arthritis and to define the immune mechanisms involved.

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  • Aberer E, Brunner C, Suchanek G, Klade H, Barbour A, Stanek G, Lassmann H. Molecular mimicry and Lyme borreliosis: a shared antigenic determinant between Borrelia burgdorferi and human tissue. Ann Neurol. 1989 Dec;26(6):732–737. [PubMed]
  • Barbour AG, Burgdorfer W, Grunwaldt E, Steere AC. Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete. J Clin Invest. 1983 Aug;72(2):504–515. [PMC free article] [PubMed]
  • Barbour AG, Heiland RA, Howe TR. 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. [PubMed]
  • Benach JL, Bosler EM, Hanrahan JP, Coleman JL, Habicht GS, Bast TF, Cameron DJ, Ziegler JL, Barbour AG, Burgdorfer W, et al. Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med. 1983 Mar 31;308(13):740–742. [PubMed]
  • Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317–1319. [PubMed]
  • Callister SM, Case KL, Agger WA, Schell RF, Johnson RC, Ellingson JL. Effects of bovine serum albumin on the ability of Barbour-Stoenner-Kelly medium to detect Borrelia burgdorferi. J Clin Microbiol. 1990 Feb;28(2):363–365. [PMC free article] [PubMed]
  • Chu HJ, Chavez LG, Jr, Blumer BM, Sebring RW, Wasmoen TL, Acree WM. Immunogenicity and efficacy study of a commercial Borrelia burgdorferi bacterin. J Am Vet Med Assoc. 1992 Aug 1;201(3):403–411. [PubMed]
  • Erdile LF, Brandt MA, Warakomski DJ, Westrack GJ, Sadziene A, Barbour AG, Mays JP. Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA. Infect Immun. 1993 Jan;61(1):81–90. [PMC free article] [PubMed]
  • Fikrig E, Barthold SW, Flavell RA. OspA vaccination of mice with established Borrelia burgdorferi infection alters disease but not infection. Infect Immun. 1993 Jun;61(6):2553–2557. [PMC free article] [PubMed]
  • Fikrig E, Barthold SW, Kantor FS, Flavell RA. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. [PubMed]
  • Fikrig E, Barthold SW, Kantor FS, Flavell RA. Long-term protection of mice from Lyme disease by vaccination with OspA. Infect Immun. 1992 Mar;60(3):773–777. [PMC free article] [PubMed]
  • Fikrig E, Barthold SW, Marcantonio N, Deponte K, Kantor FS, Flavell RA. Roles of OspA, OspB, and flagellin in protective immunity to Lyme borreliosis in laboratory mice. Infect Immun. 1992 Feb;60(2):657–661. [PMC free article] [PubMed]
  • Fikrig E, Barthold SW, Persing DH, Sun X, Kantor FS, Flavell RA. Borrelia burgdorferi strain 25015: characterization of outer surface protein A and vaccination against infection. J Immunol. 1992 Apr 1;148(7):2256–2260. [PubMed]
  • Garcia-Monco JC, Coleman JL, Benach JL. Antibodies to myelin basic protein in Lyme disease. J Infect Dis. 1988 Sep;158(3):667–668. [PubMed]
  • Hughes CA, Engstrom SM, Coleman LA, Kodner CB, Johnson RC. Protective immunity is induced by a Borrelia burgdorferi mutant that lacks OspA and OspB. Infect Immun. 1993 Dec;61(12):5115–5122. [PMC free article] [PubMed]
  • Jobe DA, Callister SM, Lim LC, Lovrich SD, Schell RF. Ability of canine Lyme disease vaccine to protect hamsters against infection with several isolates of Borrelia burgdorferi. J Clin Microbiol. 1994 Mar;32(3):618–622. [PMC free article] [PubMed]
  • Johnson RC, Kodner C, Russell M. Active immunization of hamsters against experimental infection with Borrelia burgdorferi. Infect Immun. 1986 Dec;54(3):897–898. [PMC free article] [PubMed]
  • Johnson RC, Kodner C, Russell M. Passive immunization of hamsters against experimental infection with the Lyme disease spirochete. Infect Immun. 1986 Sep;53(3):713–714. [PMC free article] [PubMed]
  • Johnson RC, Kodner CL, Russell ME. Vaccination of hamsters against experimental infection with Borrelia burgdorferi. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):45–48. [PubMed]
  • Johnson RC, Kodner C, Russell M, Duray PH. Experimental infection of the hamster with Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:258–263. [PubMed]
  • Jonsson M, Noppa L, Barbour AG, Bergström S. Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins. Infect Immun. 1992 May;60(5):1845–1853. [PMC free article] [PubMed]
  • Kazmierczak JJ, Sorhage FE. Current understanding of Borrelia burgdorferi infection, with emphasis on its prevention in dogs. J Am Vet Med Assoc. 1993 Dec 1;203(11):1524–1528. [PubMed]
  • Levy SA, Lissman BA, Ficke CM. Performance of a Borrelia burgdorferi bacterin in borreliosis-endemic areas. J Am Vet Med Assoc. 1993 Jun 1;202(11):1834–1838. [PubMed]
  • Lim LC, Liu YF, Schell K, Lovrich SD, Callister SM, Schell RF. Detection of borreliacidal antibody by using acridine orange and flow cytometry. Clin Diagn Lab Immunol. 1994 Jan;1(1):44–50. [PMC free article] [PubMed]
  • Lovrich SD, Callister SM, Lim LC, Schell RF. Seroprotective groups among isolates of Borrelia burgdorferi. Infect Immun. 1993 Oct;61(10):4367–4374. [PMC free article] [PubMed]
  • Lovrich SD, Callister SM, Schmitz JL, Alder JD, Schell RF. Borreliacidal activity of sera from hamsters infected with the Lyme disease spirochete. Infect Immun. 1991 Aug;59(8):2522–2528. [PMC free article] [PubMed]
  • Marconi RT, Konkel ME, Garon CF. Variability of osp genes and gene products among species of Lyme disease spirochetes. Infect Immun. 1993 Jun;61(6):2611–2617. [PMC free article] [PubMed]
  • Pavia CS, Kissel V, Bittker S, Cabello F, Levine S. Antiborrelial activity of serum from rats injected with the Lyme disease spirochete. J Infect Dis. 1991 Mar;163(3):656–659. [PubMed]
  • 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. [PubMed]
  • Sadziene A, Thompson PA, Barbour AG. In vitro inhibition of Borrelia burgdorferi growth by antibodies. J Infect Dis. 1993 Jan;167(1):165–172. [PubMed]
  • Sambri V, Armati S, Cevenini R. Animal and human antibodies reactive with the outer surface protein A and B of Borrelia burgdorferi are borreliacidal, in vitro, in the presence of complement. FEMS Immunol Med Microbiol. 1993 Jun;7(1):67–71. [PubMed]
  • Schaible UE, Gern L, Wallich R, Kramer MD, Prester M, Simon MM. Distinct patterns of protective antibodies are generated against Borrelia burgdorferi in mice experimentally inoculated with high and low doses of antigen. Immunol Lett. 1993 May;36(2):219–226. [PubMed]
  • Schaible UE, Kramer MD, Eichmann K, Modolell M, Museteanu C, Simon MM. 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. [PubMed]
  • Schaible UE, Wallich R, Kramer MD, Gern L, Anderson JF, Museteanu C, Simon MM. 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. [PubMed]
  • Schmitz JL, Schell RF, Hejka AG, England DM. Passive immunization prevents induction of Lyme arthritis in LSH hamsters. Infect Immun. 1990 Jan;58(1):144–148. [PMC free article] [PubMed]
  • Schmitz JL, Schell RF, Lovrich SD, Callister SM, Coe JE. Characterization of the protective antibody response to Borrelia burgdorferi in experimentally infected LSH hamsters. Infect Immun. 1991 Jun;59(6):1916–1921. [PMC free article] [PubMed]
  • Scriba M, Ebrahim JS, Schlott T, Eiffert H. The 39-kilodalton protein of Borrelia burgdorferi: a target for bactericidal human monoclonal antibodies. Infect Immun. 1993 Oct;61(10):4523–4526. [PMC free article] [PubMed]
  • Sigal LH. Cross-reactivity between Borrelia burgdorferi flagellin and a human axonal 64,000 molecular weight protein. J Infect Dis. 1993 Jun;167(6):1372–1378. [PubMed]
  • Simon MM, Schaible UE, Wallich R, Kramer MD. A mouse model for Borrelia burgdorferi infection: approach to a vaccine against Lyme disease. Immunol Today. 1991 Jan;12(1):11–16. [PubMed]
  • Simon MM, Schaible UE, Kramer MD, Eckerskorn C, Museteanu C, Müller-Hermelink HK, 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. [PubMed]
  • Steere AC. Lyme disease. N Engl J Med. 1989 Aug 31;321(9):586–596. [PubMed]
  • Steere AC, Bartenhagen NH, Craft JE, Hutchinson GJ, Newman JH, Rahn DW, Sigal LH, Spieler PN, Stenn KS, Malawista SE. The early clinical manifestations of Lyme disease. Ann Intern Med. 1983 Jul;99(1):76–82. [PubMed]
  • Steere AC, Gibofsky A, Patarroyo ME, Winchester RJ, Hardin JA, Malawista SE. Chronic Lyme arthritis. Clinical and immunogenetic differentiation from rheumatoid arthritis. Ann Intern Med. 1979 Jun;90(6):896–901. [PubMed]
  • Steere AC, Grodzicki RL, Kornblatt AN, Craft JE, Barbour AG, Burgdorfer W, Schmid GP, Johnson E, Malawista SE. The spirochetal etiology of Lyme disease. N Engl J Med. 1983 Mar 31;308(13):733–740. [PubMed]
  • Steere AC, Malawista SE. Cases of Lyme disease in the United States: locations correlated with distribution of Ixodes dammini. Ann Intern Med. 1979 Nov;91(5):730–733. [PubMed]
  • Steere AC, Malawista SE, Hardin JA, Ruddy S, Askenase W, Andiman WA. Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Ann Intern Med. 1977 Jun;86(6):685–698. [PubMed]
  • Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, Steele FM. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum. 1977 Jan-Feb;20(1):7–17. [PubMed]
  • Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med. 1987 Nov;107(5):725–731. [PubMed]
  • Stover CK, Bansal GP, Hanson MS, Burlein JE, Palaszynski SR, Young JF, Koenig S, Young DB, Sadziene A, Barbour AG. 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. [PMC free article] [PubMed]
  • Telford SR, 3rd, Fikrig E, Barthold SW, Brunet LR, Spielman A, Flavell RA. Protection against antigenically variable Borrelia burgdorferi conferred by recombinant vaccines. J Exp Med. 1993 Aug 1;178(2):755–758. [PMC free article] [PubMed]
  • Wilske B, Preac-Mursic V, Jauris S, Hofmann A, Pradel I, Soutschek E, Schwab E, Will G, Wanner G. Immunological and molecular polymorphisms of OspC, an immunodominant major outer surface protein of Borrelia burgdorferi. Infect Immun. 1993 May;61(5):2182–2191. [PMC free article] [PubMed]
  • Wilske B, Preac-Mursic V, Schierz G, Busch KV. Immunochemical and immunological analysis of European Borrelia burgdorferi strains. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):92–102. [PubMed]
  • Wilske B, Preac-Mursic V, Schierz G, Kühbeck R, Barbour AG, Kramer M. Antigenic variability of Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:126–143. [PubMed]
  • 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) of Borrelia burgdorferi. Med Microbiol Immunol. 1992;181(2):57–70. [PubMed]

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