Acquired resistance to Borrelia burgdorferi infection in the rabbit. Comparison between outer surface protein A vaccine- and infection-derived immunity.

Foley, Denise; Wang, Y P; Wu, Xiaoyang; Blanco, David R.; Lovett, Michael; Miller, James N.

doi:10.1172/jci119371

Cited by 15 publications

(22 citation statements)

References 43 publications

(59 reference statements)

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“…Passive immunization of rabbits with infection-immune rabbit serum results in complete protection against homologous challenge with cultivated organisms (13), suggesting that antibody is the major factor in this protection. We have also previously reported that infection-immune rabbits were resistent to challenge using numbers of organisms that were manyfold greater than that which could be demonstrated following immunization with either OspA (19,38) or outer membrane vesicles derived from cultivated, virulent B. burgdorferi (38). We have also recently found that B31 infection-immune rab-* Corresponding authors.…”

Section: Infect Immun 68:4189-4199 2000)mentioning

confidence: 91%

“…For challenge, the 20 B. burgdorferi B31 infection-immune rabbits and 20 naive control rabbits were bled and divided into four groups of five rabbits so that each group of five naive and five infection-immune rabbits were implant challenged with one of the four HAB strains of B. burgdorferi. For skin implantation, donor and recipient rabbits were first anesthetized with ketamine and xylazine as previously described (19). Each 5-mm skin punch from a donor rabbit (subsequently shown to be culture positive) was dissected into five 1-mm 2 pieces.…”

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confidence: 99%

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Homologous and Heterologous Borrelia burgdorferi Challenge of Infection-Derived Immune Rabbits Using Host-Adapted Organisms

Shang¹,

Wu²,

Lovett³

et al. 2001

Infect Immun

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Infect. Immun. 68:4189-4199, 2000).In this study, we have extended these findings to determine whether B31 strain infection-immune rabbits are also protected against heterologous HAB challenge. Infection-immune rabbits challenged with large numbers (>10 6 ) of homologous HAB strain B31 were completely protected from erythema migrans (EM) and skin and disseminated infection. In contrast, infection-immune rabbits challenged with heterologous HAB strains N40 and Sh-2-82 were completely susceptible to EM and skin and disseminated infection; challenge with strain 297 also resulted in EM and infection of the skin and viscera, but clearance of infection occurred 3 weeks postchallenge. These findings confirm that immunity elicited in rabbits by B31 strain infection confers complete protection against large-dose homologous HAB challenge but not against a heterologous strain.Lyme disease in humans, caused by tick transmission of the spirochete Borrelia burgdorferi, is known to result from different strains of B. burgdorferi sensu stricto and sensu lato found in different geographic regions of the world. While outer surface protein A (OspA) of B. burgdorferi, a surface protein expressed during tick adaptation, is currently being used for human vaccination (39, 43), it has been shown to possess antigenic heterogeneity among many strains (26,29,35,48). Moreover, it is now recognized that OspA is downregulated during mammalian infection and that its mechanism of protective immunity works by inhibiting B. burgdorferi growth in the tick following a blood meal from a vaccinated individual (15, 37). Furthermore, organisms that have become host adapted and no longer express OspA are not susceptible to killing by OspA-specific antibodies (7). Thus, the search for additional cross-protective immunogens has attracted considerable interest for future adjuncts to the OspA vaccine.Several experimental animal models for the study of Lyme disease pathogenesis and immunity have been utilized, including the rat (8), hamster (25), mouse (5), rabbit (18, 47), guinea pig (41), dog (10, 21), and monkey (33). With the exception of rabbits, mammalian infection with B. burgdorferi results in chronic infection in these animals (3,6,16,31,34). In the mouse model, Barthold has demonstrated that chronic infection elicits complete protection against homologous challenge and partial protection against heterologous challenge using cultivated organisms (4). However, protection studies in mice challenged with organisms acquired from infected tissues which no longer express OspA, called host adapted by Barthold and which we now refer to as host-adapted Borrelia (HAB), show only partial protection against homologous challenge and little to no protection against heterologous challenge (4). Recently, Hansen and coworkers have demonstrated that immunization of mice with decorin-binding protein A (DbpA) from strain 297, a surface protein which has been implicated in spirochetal adhesion and which is upregulated during mammalian infection, protected against homol...

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Section: Infect Immun 68:4189-4199 2000)mentioning

confidence: 91%

mentioning

confidence: 99%

Homologous and Heterologous Borrelia burgdorferi Challenge of Infection-Derived Immune Rabbits Using Host-Adapted Organisms

Shang¹,

Wu²,

Lovett³

et al. 2001

Infect Immun

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“…␣-VlsE was a gift of Steven Norris, University of Texas at Houston (unpublished data). IRS was obtained from rabbits with complete infection-derived immunity to reinfection (10,11,37). CMS was obtained from four C3H/Hej mice infected for 4 months with strain B31.…”

Section: Methodsmentioning

confidence: 99%

“…In the rabbit model of Lyme disease, B. burgdorferi infection is naturally cleared, with resulting immunity to reinfection (11). In mice, the immune response does not result in clearance of the infection, and chronic infection is established.…”

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confidence: 99%

Temporal Analysis of the Antigenic Composition of Borrelia burgdorferi during Infection in Rabbit Skin

et al. 2004

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The numbers of host-adapted Borrelia burgdorferi (HAB) organisms in rabbit skin were assessed by real-time PCR over the first 3 weeks of infection. Maximal numbers were found at day 11, while spirochete numbers decreased by more than 30-fold by day 21. The antigenic composition of HAB in skin biopsy samples was determined by use of a procedure termed hydrophobic antigen tissue Triton extraction. Immune sera from rabbits, sera from chronically infected mice, and monospecific antiserum to the antigenic variation protein, VlsE, were used to probe parallel two-dimensional immunoblots representing each time point. Individual proteins were identified using either specific antisera or by matching protein spots to mass spectrometryidentified protein spots from in vitro-cultivated Borrelia. There were significant changes in the relative expression of a variety of known and previously unrecognized HAB antigens during the 21-day period. OspC and the outer membrane proteins OspA and OspB were prominent at the earliest time point, day 5, when the antigenic variation protein VlsE was barely detected. OspA and OspB were not detected after day 5. OspC was not detected after day 9. VlsE was the most prominent antigen from day 7 through day 21. BmpA, ErpN, ErpP, LA7, OppA-2, DbpA, and an unidentified 15-kDa protein were also detected from day 7 through day 21. Immunoblot analysis using monospecific anti-VlsE revealed the presence of prominent distinct VlsE lower forms in HAB at days 9, 11, and 14; however, these lower forms were no longer detected at day 21. This marked diminution in VlsE lower forms paralleled the clearance of the spirochete from skin.

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“…We have previously reported that intradermal infection of the rabbit with B. burgdorferi uniformly results in the development of erythema migrans (EM) (28,29) and, in the first week of infection, dissemination to spleen, liver, lymph nodes, central nervous system, and joints. Within 3 months, B. burgdorferi infection is fully cleared, and in contrast to the mouse model (6), complete infection-derived immunity results (28) without the need for antibacterial treatment.…”

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confidence: 99%

Comparison of Protection in Rabbits against Host-Adapted and CultivatedBorrelia burgdorferifollowing Infection-Derived Immunity or Immunization with Outer Membrane Vesicles or Outer Surface Protein A

Shang

Champion

et al. 2000

Infect Immun

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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 ؋ 10 4 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 10 8 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.

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Acquired resistance to Borrelia burgdorferi infection in the rabbit. Comparison between outer surface protein A vaccine- and infection-derived immunity.

Cited by 15 publications

References 43 publications

Homologous and Heterologous Borrelia burgdorferi Challenge of Infection-Derived Immune Rabbits Using Host-Adapted Organisms

Homologous and Heterologous Borrelia burgdorferi Challenge of Infection-Derived Immune Rabbits Using Host-Adapted Organisms

Temporal Analysis of the Antigenic Composition of Borrelia burgdorferi during Infection in Rabbit Skin

Comparison of Protection in Rabbits against Host-Adapted and CultivatedBorrelia burgdorferifollowing Infection-Derived Immunity or Immunization with Outer Membrane Vesicles or Outer Surface Protein A

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