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Infection and Immunity, July 2000, p. 4189-4199, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Comparison of Protection in Rabbits against Host-Adapted and Cultivated Borrelia burgdorferi following Infection-Derived Immunity or Immunization with Outer Membrane Vesicles or Outer Surface Protein A

Ellen S. Shang,1,* Cheryl I. Champion,1 Xiao-Yang Wu,1 Jonathan T. Skare,2 David R. Blanco,1,3 James N. Miller,1,* and Michael A. Lovett3

Department of Microbiology and Immunology1 and Division of Infectious Diseases, Department of Medicine,3 School of Medicine, University of California, Los Angeles, California 90095, and Department of Medical Microbiology and Immunology, Texas A&M University, College Station, Texas 778432

Received 3 February 2000/Returned for modification 8 March 2000/Accepted 10 April 2000

In this study, infection-derived immunity in the rabbit model of Lyme disease was compared to immunity following immunization with purified outer membrane vesicles (OMV) isolated from Borrelia burgdorferi and recombinant outer surface protein A (OspA). Immunization of rabbits with OMV isolated from virulent strain B31 and its avirulent derivative B313 (lacking OspA and DbpA) conferred highly significant protection against intradermal injection with 6 × 104 in vitro-cultivated virulent B. burgdorferi. This is the first demonstration of protective immunogenicity induced by OMV. While immunization with OspA and avirulent B31 OMV provided far less protection against this challenge, rabbits with infection-derived immunity were completely protected. Protection against host-adapted B. burgdorferi was assessed by implantation of skin biopsies taken from rabbit erythema migrans (a uniquely rich source of B. burgdorferi in vertebrate tissue) containing up to 108 spirochetes. While all of the OMV- and OspA-immunized rabbits were fully susceptible to skin and disseminated infection, rabbits with infection-derived immunity were completely protected. Analysis of the antibody responses to outer membrane proteins, including DbpA, OspA, and OspC, suggests that the remarkable protection exhibited by the infection-immune rabbits is due to antibodies directed at antigens unique to or markedly up-regulated in host-adapted B. burgdorferi.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, UCLA School of Medicine, 10833 Le Conte Ave. CHS 43-239, Los Angeles, CA 90095. Phone: (310) 825-4188 (Ellen S. Shang) or (310) 825-1979 (James N. Miller). Fax: (310) 267-2265. E-mail: eshang{at}microimmun.medsch.ucla.edu (Ellen S. Shang) or jmiller{at}microimmun.medsch.ucla.edu (James N. Miller).

Infection and Immunity, July 2000, p. 4189-4199, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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