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Gern, Lise

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Gern, Lise
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Ancien.ne collaborateur.trice
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https://libra.unine.ch/handle/123456789/303

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  • Publication
    Métadonnées seulement
    Apodemus species mice are reservoir hosts of Borrelia garinii OspA serotype 4 in Switzerland
    (2002)
    Hügli, Delphine
    ;
    Hu, Chang Min
    ;
    Humair, Pierre-François
    ;
    Wilske, Bettina
    ;
    Gern, Lise 
    Among Borrelia burgdorferi sensu lato isolates, seven outer surface protein A (OspA) serotypes have been described: serotypes 1 and 2 correspond to B. burgdorferi sensu stricto and Borrelia afzelii, respectively, and serotypes 3 to 7 correspond to Borrelia garinii. In Europe, serotype 4 has never been isolated from Ixodes ricinus ticks until recently, although this serotype has been frequently isolated from cerebrospinal fluid from patients. In Europe, B. afzelii and B. burgdorferi sensu stricto were found associated with rodents and B. garinii was found associated with birds. In this study, the reservoir role of Apodemus mice for B. garinii OspA serotype 4 was demonstrated by xenodiagnosis. Apodemus mice are the first identified reservoir hosts for B. garinii OspA serotype 4.
  • Publication
    Métadonnées seulement
    Dynamics of dissemination and outer surface protein expression of different European Borrelia burgdorferi sensu lato strains in artificially infected Ixodes ricinus nymphs
    (2002)
    Fingerle, Volker
    ;
    Rauser, Sandra
    ;
    Hammer, Bettina
    ;
    Kahl, Olaf
    ;
    Heimerl, Christiane
    ;
    Schulte-Spechtel, Ulrike
    ;
    Gern, Lise 
    ;
    Wilske, Bettina
    Unfed Ixodes ricinus nymphs were infected with eight different strains and clones of Borrelia afzelii and B. garinii by capillary feeding. Except one B. afzelii clone, all expressed OspC in culture. Tick midguts and salivary glands were investigated at different time intervals for the presence of borreliae and for OspA and OspC phenotypes by immunofluorescence with simultaneous staining of OspA and OspC with monoclonal antibodies. Both species were transmittable to L ricinus. All OspC-expressing strains and clones were able to disseminate into the salivary glands. In contrast, the OspC-negative B. afzelii clone was not detectable in the salivary glands, an indication that OspC plays an important role in dissemination. OspA-positive borreliae prevailed in the midgut. OspC positives were more frequent in the salivary glands than in the midgut. Notably, simultaneously OspA- and OspC-negative borreliae were detected in both organs. Kinetics of dissemination varied with the strains. The OspC-positive B. afzelii clone and all B. garinii OspA type 4 strains were detectable in the salivary glands right after feeding, while one B. garinii OspA type 6 strain invaded the salivary glands with a delay of 24 h. These findings support the hypothesis that OspA is abundantly expressed in unfed ticks while upregulation of OspC is also a prerequisite for dissemination in the vector for the Eurasian species B. afzelii and B. garinii. However, we found strain-specific dynamics of Osp expression and strain-specific kinetics of systemic infection in the vector tick and it appears that additional factors are involved in the initiation and regulation of the dissemination process.
  • Publication
    Métadonnées seulement
    Transmission of Borrelia garinii OspA serotype 4 to BALB/c mice by Ixodes ricinus ticks collected in the field
    (2001)
    Hu, Chang Min
    ;
    Wilske, Bettina
    ;
    Fingerle, Volker
    ;
    Lobet, Yves
    ;
    Gern, Lise 
    In Europe, Borrelia garinii OspA serotype 4 has been isolated from the cerebrospinal fluid of patients but, up to now, has never been identified among culture isolates from Ixodes ricinus ticks. This information raises the question of whether OspA serotype 4 is transmitted by I. ricinus in nature. In the present study, L ricinus nymphs collected in an area of endemicity in southern Germany were allowed to feed on mice. Cultivation of ear biopsy specimens showed that six of seven B. garinii-infected mice were infected by OspA serotype 4. In contrast, very few B. garinii OspA serotype 4 organisms were isolated directly from the ticks which infected the mice; most isolates were B. afzelii. The infected mice transmitted mainly OspA serotype 4 to xenodiagnostic ticks, preferentially in combination with B. afzelii.
  • Publication
    Métadonnées seulement
    Resolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC
    (1999)
    Zhong, Weimin
    ;
    Gern, Lise 
    ;
    Stehle, Thomas
    ;
    Museteanu, Crisan
    ;
    Kramer, Michael
    ;
    Wallich, Reinhard
    ;
    Simon, Markus M
    Vaccination with outer surface protein A (OspA) of Borrelia burgdorferi prevents subsequent infection and disease in both laboratory animals and humans with high efficacy. OspA-based immunity, however, does not affect established infection due to the loss of OspA expression in the vertebrate host. We show here that repeated passive transfer of mouse and/or rabbit immune sera to recombinant GST-OspC fusion protein resulted in a dose-dependent resolution (1) of fully established arthritis and carditis as well as infection in needle-challenged C.B-17 SCID and (2) of infection in both experimentally and tick-infected BALB/c mice. Unexpectedly, active immunization of disease-susceptible AKR/N mice with GST-OspC only led to prevention but not resolution of disease and infection, in spite of high serum titers of OspC-specific Ab and the expression of ospC in tissue-derived spirochetes. The data suggest that the efficacy of OspC antibody-mediated immunity depends on the immunological history of the recipient and/or environment-dependent regulation of OspC surface expression by spirochetes in vivo. The results encourage further attempts to develop therapeutic vaccination protocols against Lyme disease.
  • Publication
    Métadonnées seulement
    Therapeutic passive vaccination against chronic Lyme disease in mice
    (1997)
    Zhong, Weimin
    ;
    Stehle, Thomas
    ;
    Museteanu, Crisan
    ;
    Siebers, Annette
    ;
    Gern, Lise 
    ;
    Kramer, Michael
    ;
    Wallich, Reinhard
    ;
    Simon, Markus M
    Passive and active immunization against outer surface protein A (OspA) has been successful in protecting laboratory animals against subsequent infection with Borrelia burgdorferi. Antibodies (Abs) to OspA convey full protection, but only when they are present at the time of infection, Abs inactivate spirochetes within the tick and block their transmission to mammals, but do not affect established infection because of the loss of OspA in the vertebrate host. Our initial finding that the presence of high serum titers of anti-OspC Abs (5 to 10 mu g/ml) correlates with spontaneous resolution of disease and infection in experimentally challenged immunocompetent mice suggested that therapeutic vaccination with OspC may be feasible. We now show that polyclonal and monospecific mouse immune sera to recombinant OspC, but not to OspA, of B. burgdorferi resolve chronic arthritis and carditis and clear disseminated spirochetes in experimentally infected C.B.-17 severe combined immunodeficient mice in a dose-dependent manner. This was verified by macroscopical and microscopical examination of affected tissues and recultivation of spirochetes from ear biopsies. Complete resolution of disease and infection was achieved, independent of whether OspC-specific immune sera (10 mu g OspC-specific Abs) were repeatedly given (4 x in 3- to 4-day intervals) before the onset (day 10 postinfection) or at the time of fully established arthritis and carditis (days 19 or 60 postinfection). The results indicate that in mice spirochetes constitutively express OspC and are readily susceptible to protective OspC-specific Abs throughout the infection. Thus, an OspC-based vaccine appears to be a candidate for therapy of Lyme disease.
  • Publication
    Métadonnées seulement
    Immunization with a polyvalent OspA vaccine protects mice against Ixodes ricinus tick bites infected by Borrelia burgdorferi ss, Borrelia garinii and Borrelia afzelii
    (1997)
    Gern, Lise 
    ;
    Hu, Chang Min
    ;
    Voet, Pierre
    ;
    Hauser, Pierre
    ;
    Lobet, Yves
    Sequence variability of the outer surface protein (Osp) A among Borrelia burgdorferi sl species suggests that a monovalent OspA vaccine may not protect against the various Borrelia present in Eurasia. Here, we confirmed that a monovalent recombinant OspA (rOspA) vaccine noes not protect mice against Ixodes ricinus mediated infection with B. burgdorferi ss, Borrelia garinii and Borrelia afzelii. However when mice were vaccinated with a cocktail of various rOspA from these three species, they were protected, and all challenge ricks that fed on them were cleared of their spirochetes. These results showed that a multiple OspA antigens vaccine, compatible with human use, was very efficient at protecting mice against B. burgdorferi ss, B. garinii and B. afzelii. (C) 1997 Elsevier Science Ltd.
  • Publication
    Métadonnées seulement
    Apodemus sp. rodents, reservoir hosts for Borrelia afzelii in an endemic area in Switzerland
    (1997)
    Hu, Chang Min
    ;
    Humair, Pierre-François
    ;
    Wallich, Reinhard
    ;
    Gern, Lise 
    Borrelia burgdorferi is maintained in nature in transmission cycles alternatively involving ticks and reservoir hosts. Small rodents like Apodemus mice and Clethrionomys voles are the primary reservoir of Lyme disease in Europe. In this study, we analyzed by SDS-PAGE and Western blot 20 borrelial isolates from xenodiagnostic ticks fed on four Apodemus sp. mice captured in the Staatswald forest (Switzerland). All isolates but one showed a homogeneous protein pattern expressing an outer surface protein, (Osp) A of 32 kDa and an OspB of 35 kDa and reacted with monoclonal antibody (mAb) I 17.3 specific for B. afzelii. One isolate expressed an OspA of 32.5 kDa and an OspB of 35 kDa and did not react with species-specific mAbs I 17.3, D6 and H3TS, but was shown to belong to B., afzelii by Southern blot analysis. The possibility exists that non-cultivatable borreliae are present in xenodiagnostic ticks. However, our results clearly show that Apodemus sp. are reservoir hosts for B. afzelii, since this genospecies is transmitted from Apodemus sp. to feeding larval ticks.
  • Publication
    Métadonnées seulement
    T helper cell priming of mice to Borrelia burgdorferi OspA leads to induction of protective antibodies following experimental but not tick-borne infection
    (1997)
    Zhong, Weimin
    ;
    Gern, Lise 
    ;
    Kramer, Michael
    ;
    Wallich, Reinhard
    ;
    Simon, Markus M
    Antibodies to the outer surface lipoprotein A (OspA) of Borrelia burgdorferi confer protection to SCID mice against subsequent tick-borne or experimental infection. However, OspA-specific antibodies are hardly detectable in naturally infected humans, dogs, hamsters and mice. This is most probably due to limited expression of OspA on spirochetes transmitted from the vector to the host. Here we have tested whether T cell priming of mice would lead to the induction of protective OspA-specific antibodies upon infection. It is shown that AKR/N mice, previously immunized with either a single T helper cell peptide of OspA, or a mixture of 27 peptides spanning the entire molecule, develop OspA-specific IgM or IgG antibodies, including those to a prominent protective B cell epitope of OspA, LA-2, within 7 days of infection with low doses (10(3)) of culture-derived spirochetes. In marked contrast, the same groups of pre-sensitized mice failed to generate any detectable OspA-specific antibodies after tick-borne infection for more than 40 days after infection. All mice, irrespective of their state of T cell immunity to OspA or the mode of infection, produced similar levels of OspC-specific IgM and IgG antibodies as early as day 14 after infection. None of the mice previously immunized with OspA peptides were protected against experimental infection, in spite of the appearance of protective antibodies. It is clear from these data that, in contrast to culture-derived spirochetes, the naturally transmitted pathogen fails to express OspA within the mammalian host at levels sufficient for induction of B cell responses, even in the presence of pre-activated T helper cells. Together with the fact that OspA-specific antibodies are mainly operative by eliminating spirochetes from the vector during infestation, the data suggest that OspA-vaccination for T helper cell immunity alone is not sufficient to prevent Lyme disease.