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Infection and Immunity, February 2000, p. 658-663, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Occurrence of Severe Destructive Lyme Arthritis in Hamsters Vaccinated with Outer Surface Protein A and Challenged with Borrelia burgdorferi

Cindy L. Croke,1,2 Erik L. Munson,1,2 Steven D. Lovrich,3 John A. Christopherson,1,2 Monica C. Remington,1,2 Douglas M. England,4,5 Steven M. Callister,3,6 and Ronald F. Schell1,2,7,*

Wisconsin State Laboratory of Hygiene1 and Departments of Medical Microbiology and Immunology,2 Bacteriology,7 and Pathology and Laboratory Medicine,4 University of Wisconsin, Madison, Wisconsin 53706; Department of Pathology, Meriter Hospital, Madison, Wisconsin 537155; and Microbiology Research Laboratory3 and Section of Infectious Diseases,6 Gundersen Lutheran Medical Center, La Crosse, Wisconsin 54601

Received 31 August 1999/Returned for modification 27 October 1999/Accepted 10 November 1999

Arthritis is a frequent and major complication of infection with Borrelia burgdorferi sensu stricto. The antigens responsible for the induction of arthritis are unknown. Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 µg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B. burgdorferi sensu stricto isolate 297 or C-1-11. Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 µg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection with B. burgdorferi sensu stricto. When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge with B. burgdorferi sensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged with B. burgdorferi sensu stricto. These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans.

* Corresponding author. Mailing address: Wisconsin State Laboratory of Hygiene, University of Wisconsin, 465 Henry Mall, Madison, WI 53706. Phone: (608) 262-3634. Fax: (608) 265-3451. E-mail: rfschell{at}facstaff.wisc.edu.

Infection and Immunity, February 2000, p. 658-663, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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