Wisconsin State Laboratory ofHygiene,' and Departments of Bacteriology,2 Medical ... Gundersen Medical Foundation, La Crosse, Wisconsin 546016. Received ...
INFECTION AND IMMUNITY,
0019-9567/94/$04.00+0
Vol. 62, No. 7
JUlY 1994, p. 2825-2833
Copyright C 1994, American Society for Microbiology
Development of Destructive Arthritis in Vaccinated Hamsters Challenged with Borrelia burgdorferi LONY C. L. LIM,"2 DOUGLAS M. ENGLAND,3'4 BRIAN K DuCHATEAU,1'2 NICOLE J. GLOWACKI,1'2 JENNIFER R. CRESON,1'2 STEVEN D. LOVRICH,6 STEVEN M. CALLISTER,6 DEAN A. JOBE,6 AND RONALD F. SCHELL' 2,5* and State Departments of Bacteriology,2 Medical Microbiology and Immunology,' Wisconsin Laboratory of Hygiene,' and Pathology and Laboratory Medicine,3 University of Wisconsin, Madison, Wisconsin 53706; Department of Pathology, Meriter Hospital, Madison, Wisconsin 537154; and Microbiology Research Laboratory, Gundersen Medical Foundation, La Crosse, Wisconsin 546016 Received 15 December 1993/Returned for modification 15 February 1994/Accepted 14 April 1994
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-i-li in adjuvant. A severe destructive arthritis was readily evoked in vaccinated hamsters challenged with the homologous B. burgdorferi sensu stricto isolate C-i-li before high levels of protective borreliacidal antibody developed. Once high levels of C-i-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. burgdorfieri sensu lato (B. burgdorfefi sensu stricto isolate 297, Borrelia garinii isolate LV4, and Borrelia afzelii isolate BV1) despite high levels of C-i-il 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. tant concerns about the heterogenicity (4, 15, 24, 31, 56-59)
Lyme borreliosis is caused by the spirochete Borrelia burgdorfeie sensu lato (3, 5, 19) and is transmitted primarily to human hosts by Ixodes ticks (6, 49, 50). Its most characteristic clinical feature is an expanding skin lesion, erythema migrans, yet patients with the illness may present with arthritic, cardiac, or neurological symptoms without a skin lesion (46, 47, 53). The signs and symptoms of the disease change frequently and are often intermittent. If the infection is left untreated, chronic arthritis may develop in weeks or months. Today, Lyme borreliosis has become the most frequently reported tickassociated illness in the United States (8) since it was first consistently reported in the 1970s (48, 51, 52). The high level of interest in Lyme borreliosis has facilitated a worldwide effort to develop an effective vaccine against B. burgdorferi sensu lato. The feasibility of vaccination has been demonstrated in dogs (9, 26), gerbils (33), hamsters (17, 18, 20), and mice (12, 13, 43, 44, 54, 55). Viable (21, 23, 30, 32, 36, 39, 40) and nonviable (9, 17, 18, 20, 22, 26) Lyme borreliosis spirochetes and several of their outer surface proteins, including OspA (12, 13, 34, 35, 37, 38, 43, 44, 54, 55), OspB (14, 34, 35, 55), OspC (33), and the 39-kDa protein (41), have been shown to induce protective antibodies capable of killing isolates of B. burgdorferi sensu lato in vitro or preventing infection
and immunogenicity (10, 54) of nonviable whole spirochetes and subunit components. In addition, the possibility of adverse effects developing from vaccination with or without adjuvants must be considered. In this study, we present the first direct evidence that an adverse effect, especially severe destructive arthritis, can develop after vaccination against the Lyme borreliosis spirochete. We describe the development of severe destructive arthritis in mature immunocompetent hamsters vaccinated with a wholecell preparation of Formalin-inactivated B. burgdorferi sensu lato in adjuvant after challenge with isolates of the three genomic groups of B. burgdorfer sensu lato. MATERIALS AND METHODS Hamsters. Six- to 8-week-old inbred LSH/Ss WSLH hamsters were obtained from our breeding colony located at the
Wisconsin State Laboratory of Hygiene. Hamsters weighing 60 to 120 g were housed three per cage at an ambient temperature of 21°C. Food and water were available ad libitum. Organisms. Low-passage (
