Occurrence of severe destructive lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi.
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 microg 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 microg 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.
Croke
C L
CL
Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin 53706, USA.
Munson
E L
EL
Lovrich
S D
SD
Christopherson
J A
JA
Remington
M C
MC
England
D M
DM
Callister
S M
SM
Schell
R F
RF
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D006224:Cricetinae; D008074:Lipoproteins; D008193:Lyme Disease / Q000209:etiology* / Q000473:pathology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein; D014614:Vaccines, Synthetic