Immune sera to individual Borrelia burgdorferi isolates or recombinant OspA thereof protect SCID mice against infection with homologous strains but only partially or not at all against those of different OspA/OspB genotype

Schaible, Ulrich E.; Wallich, R; Kramer, Michael D.; Gern, Lise; Anderson, John F.; Museteanu, C; Simon, Markus M.

doi:10.1016/0264-410x(93)90132-h

Cited by 57 publications

(40 citation statements)

References 25 publications

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“…The reason for this is the fact that the two routes of spirochete inoculation, i.e. tick versus needle infection, lead to greatly differing courses of infection, induction of immune responses and onset of disease manifestations [23,25,55]. However, it is clear that only the natural mode of infection will uncover strategies of either spirochetes or mammals which are of biological significance and thus of relevance for the appropriate treatment of Lyme disease.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Lederer

Brenner

Stehlé

et al. 2004

Med Microbiol Immunol

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Adaptation of Borrelia burgdorferi in the vector and vertebrate host is mediated by mechanisms that regulate differential expression of outer surface lipoproteins (Osps). In this study, real time PCR was applied to quantify tissue-specific expression of four linear plasmid (lp54)-encoded (ospA, zs7.a36, zs7.a66 zs7.a68) and one circular plasmid (cp26)-encoded (ospC) gene from B. burgdorferi sensu stricto, in a natural setting of tick-infected immunodeficient (C.B-17 SCID) and immunocompetent (BALB/c and AKR/OlaHsd) mice for up to 120 days post-infection (p.i.). Early during infection (day 30 p.i.) high numbers of spirochetes were found in the heart and joint, but not the ear and spleen tissues of disease-susceptible SCID mice. In diseasesusceptible AKR mice spirochetes colonized the ear and joint tissues, but were undetectable in tissues of diseaseresistant BALB/c mice. Later in infection (day 120 p.i.), spirochetes had expanded ($1,000-fold) in all SCID tissues tested but were undetectable in AKR and BALB/ c mice. Of the five genes analyzed, only zs7.a36 transcripts were detected in various tissues of all infected mouse strains, though at differing levels, whereas ospC transcripts were only found in tissue specimens of SCID mice. Furthermore, gene expression of ospC and zs7.a36 appears to be differentially regulated in distinct organs of individual mice. In contrast, transcripts for ospA, zs7.a66, and zs7.a68 were not detected in any of the mouse strains, independent of their immune status and/ or the severity of their infection/inflammatory responses. Late during infection (day 120 p.i.), transcription of zs7.a36 and ospC was down-regulated in the tissues of SCID mice despite expansion of spirochetes. This type of quantitative analysis may be helpful to further disclose principles of pathogenesis of Lyme borreliosis and to design strategies for its therapeutic treatment.

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Section: Discussionmentioning

confidence: 99%

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Lederer

Brenner

Stehlé

et al. 2004

Med Microbiol Immunol

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“…It has been shown by Johnson et al [20] that whole cell vaccines derived from different strains are not necessarily cross-protective. Various authors demonstrated lack of cross-protection for OspA vaccines derived from different strains, some demonstrated that this was associated with differences in the OspA sequence [17,25,26,35]. In addition, it has been shown that a neutralizing OspA epitope is recognized by a type-specific mAb [34,42].…”

Section: Discussionmentioning

confidence: 99%

Diversity of OspA and OspC among cerebrospinal fluid isolates ofBorrelia burgdorferi sensu lato from patients with neuroborreliosis in Germany

Wilske

Busch

Eiffert

et al. 1996

Med Microbiol Immunol

108

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Neuroborreliosis is the most frequent manifestation of the second stage of Lyme borreliosis in Europe. However, only few isolates from the cerebrospinal fluid (CSF) have been characterized with controversial results. A large panel of 36 CSF isolates isolated over a 10-year period in Munich has now been analyzed for their OspA and OspC type, resulting in at least eight different types, respectively. Representatives of the different types cultivated from CSF in Munich have also been isolated from other geographical regions in Europe from CSF or ticks, suggesting a widespread distribution of pathogenic strains. A certain OspA type (type 4) was frequently observed in adults but rarely in children or ticks. Since OspA and OspC are the most promising candidates for a Borrelia vaccine, the considerable heterogeneity found among CSF isolates has important implications for development of a vaccine in Europe.

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“…and 1 h later, the recipients were challenged experimentally (s.c.) with lo5 B. burgdorferi ZS7. Mice were monitored for the development of clinical arthritis under blinded conditions and for the presence of spirochetes by cultivating ear biopsies in BSK medium after 27 days as described [9,34]. The development of clinical arthritis in the tibiotarsal joints was scored as described [35] using swelling and reddening as criteria: + + , severe; +, prominent; (+), moderate; +/-, mild; (+/-), mainly reddening without significant swelling; and -, no clinical signs of arthritis.…”

Section: Passive Protectionmentioning

confidence: 99%

Protective immunization with plasmid DNA containing the outer surface lipoprotein A gene of Borrelia burgdorferi is independent of an eukaryotic promoter

et al. 1996

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Plasmid DNA encoding the outer surface lipoprotein A (OspA) of Borrelia burgdorferi under the control of either strong eukaryotic/viral or its own bacterial promoter was injected intramuscularly (m. tibialis anterior) or intradermally into BALB/c and AKR/N mice. OspA-specific antibodies and OspA-reactive T helper 1 cells (Th1) were induced only with those plasmids containing the ospA structural gene including its own regulatory control region immediately upstream. In the absence of the ospA promoter, no or only marginal immune responses to OspA were obtained, even when strong eukaryotic promoter/enhancer elements were present. Together with the finding that the ospA promoter is active in a mouse B-lymphoma line, the data suggest that spirochetes are able to express at least part of their genes in the mammalian environment. Mice previously vaccinated with the relevant ospA plasmid DNA were protected against subsequent experimental challenge with a virulent strain of B. burgdorferi, as measured by the appearance of antibodies to a prominent protective epitope (LA-2) and the failure to re-isolate spirochetes from ear biopsies. In addition, C.B-17 severe-combined immunodeficient mice could be protected against infection by passive transfer of immune sera from ospA plasmid DNA-inoculated normal mice. Protective LA-2-related antibody titers obtained after repeated immunization persisted for 200 days and longer. This simple procedure of immunization using plasmid DNA consisting of a prokaryotic gene under the control of its own promoter holds great promise for the development of alternative subunit vaccines against bacterial infections, including Lyme disease. In addition, the availability of this novel prokaryotic promoter element now allows the study of the basis for the differential expression of bacterial genes in prokaryotic and eukaryotic environments.

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Immune sera to individual Borrelia burgdorferi isolates or recombinant OspA thereof protect SCID mice against infection with homologous strains but only partially or not at all against those of different OspA/OspB genotype

Cited by 57 publications

References 25 publications

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Diversity of OspA and OspC among cerebrospinal fluid isolates ofBorrelia burgdorferi sensu lato from patients with neuroborreliosis in Germany

Protective immunization with plasmid DNA containing the outer surface lipoprotein A gene of Borrelia burgdorferi is independent of an eukaryotic promoter

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