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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
    Artificial-infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease
    (2003)
    Wallich, Reinhard
    ;
    Jahraus, Oliver
    ;
    Stehle, Thomas
    ;
    Tran, Thi Thanh Thao
    ;
    Brenner, Christiane
    ;
    Hofmann, Heidelore
    ;
    Gern, Lise 
    ;
    Simon, Markus M
    Vaccination with recombinant outer surface protein A (OspA) from Borrelia burgdorferi provides excellent antibody-mediated protection against challenge with the pathogen in animal models and in humans. However, the bactericidal antibodies are ineffective in the reservoir host, since OspA is expressed by spirochetes only in the vector, but rarely, if at all, in mammals. Using an artificially generated immune serum (anti-10(8) spirochetes) with high protective potential for prophylactic and therapeutic treatment, we have now isolated from an expression library of B. burgdorferi (strain ZS7) three novel genes, zs7.a36, zs7.a66 and zs7.a68. All three genes are located, together with ospA/B, on the linear plasmid lp54, and are expressed in vitro and in ticks. At least temporarily two of them, ZS7.A36 and ZS7.A66, are also expressed during infection. The respective natural antigens are poorly immunogenic in infected normal mice but elicited antibodies in Lyme disease patients. We show that recombinant preparations of ZS7.A36, ZS7.A66 and ZS7.A68 induce functional antibodies in rabbits capable of protecting immunodeficient mice against subsequent experimental infection. These findings suggest that all three recombinant antigens represent potential candidates for a 'second generation' vaccine to prevent and/or cure Lyme disease.
  • Publication
    Métadonnées seulement
    Lyme disease
    (2000)
    Gern, Lise 
    ;
    Falco, Richard C
    Lyme borreliosis, the most common vector-borne disease in the northern hemisphere, is caused by bacteria belonging to the Borrelia burgdorferi complex. The disease is multisystemic, affecting main ly the skin, nervous system, heart and joints. in Europe, the vector of the disease is the tick Ixodes ricinus, whereas in the United States of America, two primary tick vectors exist, namely: I. scapularis in the north-eastern and mid-western regions and I. pacificus on the west coast. Several species of small and medium-sized mammals and ground-feeding birds serve as reservoirs for the bacteria in endemic areas. The prognosis for patients with Lyme borreliosis is excellent, particularly when diagnosed and treated early in the course of infection. Prevention of Lyme borreliosis can be achieved using two approaches, either prevention of infection by immunisation, or prevention of tick bites through avoidance, personal protection and tick control.
  • 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
    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
    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.
  • Publication
    Accès libre
    Ixodes (Pholeoixodes) hexagonus, an efficient vector of Borrelia burgdorferi in the laboratory
    (1991)
    Gern, Lise 
    ;
    Toutoungi, L. N.
    ;
    Hu, Chang Min
    ;
    Aeschlimann, André 
    Borrelia burgdorferi Johnson et al. was first isolated from the midgut of Ixodes dammini Spielman et al. in the U.S.A. and from the midgut of Lricinus (L.) in Europe. I.ricinus was considered to be the only tick vector of this borrelia, in Europe, until I.hexagonus Leach, the hedgehog tick, was found to harbour spirochaetes. This paper reports an evaluation of the vector competence of I. hexagonus for the spirochaete B. burgdorferi. Transovarial and trans-stadial survival were demonstrated and the spirochaete was transmitted to laboratory mice via the bites of trans-stadially infected I.hexagonus females.
  • Publication
    Accès libre
    Lyme disease
    Gern, Lise 
    ;
    Falco, R.C
    La borréliose de Lyme qui est, dans l'hémisphère nord, la plus répandue des maladies à transmission vectorielle, est due à des bactéries appartenant au genre Borrelia burgdorferi. Il s'agit d'une maladie plurisystémique qui affecte essentiellement la peau, le système nerveux le cœur et les articulations. En Europe, le vecteur de la maladie est la tique Ixodes ricinus; aux États -Unis d'Amérique les deux vecteurs principaux sont la tique I. scapularis dans les régions du nord-est et du centre-ouest et I. pacificus sur la Côte Ouest. Plusieurs espèces de petits et moyens mammifères ou d'oiseaux terrestres servent de réservoirs à la bactérie dans les zones endémiques. Le pronostic est excellent, surtout lorsque la maladie de Lyme est diagnostiquée en phase initiale et traitée immédiatement. La prophylaxie repose sur deux méthodes: l'immunisation préventive, d'une part, et la mise en œuvre de mesures permettant d'éviter les piqûres de tiques et de lutter contre ces vecteurs, d'autre part., Lyme borreliosis, the most common vector-bome disease in the northern hemisphere, is caused by bacteria belonging to the Borrelia burgdorferi complex. The disease is multisystemic, affecting mainly the skin, nervous system, heart and joints. In Europe, the vector of the disease is the tick Ixodes ricinus, whereas in the United States of America, two primary tick vectors exist, namely: I. scapularis in the north-eastern and mid-western regions and I. pacificus on the west coast. Several species of small and medium-sized mammals and ground-feeding birds serve as reservoirs for the bacteria in endemic areas. The prognosis for patients with Lyme borreliosis is excellent, particularly when diagnosed and treated early in the course of infection. Prevention of Lyme borreliosis can be achieved using two approaches, either prevention of infection by immunisation, or prevention of tick bites through avoidance, personal protection and tick control., De todas las enfermedades vehiculadas por vectores, la borreliosis de Lyme, causada por bacterias pertenecientes al complejo Borrelia burgdorferi, es la más común en el hemisferio norte. Esta enfermedad de carácter multisistémico afecta principalmente la piel, el sistema nervioso, el corazón y las articulaciones. En Europa, el vector de la enfermedad es la garrapata Ixodes ricinus. En los Estados Unidos de América, por su parte, existen dos garrapatas que ejercen de vectores primarios: I.scapularis en las regiones del noreste y el medio oeste, e I.pacificus en la costa oeste. En las áreas endémicas varias especies de mamíferos pequeños y medianos y de aves de alimentación terrestre sirven de reservorio de las bacterias. Los pacientes afectados de borreliosis de Lyme presentan un pronóstico excelente, sobre todo cuando se diagnostica y trata la infección en sus fases iniciales. Para prevenir esta enfermedad caben dos procedimientos distintos: prevenir la infección con medidas de inmunización; o impedir la mordedura de la garrapata previniendo esta posibilidad, protegiéndose del contacto y luchando contra sus poblaciones.
  • Publication
    Accès libre
    Protective immunization with plasmid DNA containing the outer surface lipoprotein A gene of Borrelia burgdorferi is independent of an eukaryotic promoter
    Simon, Markus M
    ;
    Gern, Lise 
    ;
    Hauser, Pierre
    ;
    Zhong, Weimin
    ;
    Nielsen, Peter J
    ;
    Kramer, Michael D
    ;
    Brenner, Christiane
    ;
    Wallich, Reinhard
    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.
  • Publication
    Accès libre
    T helper cell priming of mice to Borrelia burgdorferi Osp A leads to induction of protective antibodies following experimental but not tickborne infection
    Zhong, Weimin
    ;
    Gern, Lise 
    ;
    Kramer, Michael
    ;
    Wallich, Reinhard
    ;
    Simon, Markus M
    Antibodies to the outer surface lipoprotein A (Osp A) of Borrelia burgdorferi confer protection to SCID mice against subsequent tick-borne or experimental infection. However, Osp A-specific antibodies are hardly detectable in naturally infected humans, dogs, hamsters and mice. This is most probably due to limited expression of Osp A 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 Osp A-specific antibodies upon infection. It is shown that AKR/N mice, previously immunized with either a single T helper cell peptide of Osp A, or a mixture of 27 peptides spanning the entire molecule, develop Osp A-specific IgM or IgG antibodies, including those to a prominent protective B cell epitope of Osp A, LA-2, within 7 days of infection with low doses (103) of culture-derived spirochetes. In marked contrast, the same groups of pre-sensitized mice failed to generate any detectable Osp A-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 Osp C-specific IgM and IgG antibodies as early as day 14 after infection. None of the mice previously immunized with Osp A 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 Osp A 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 Osp A-specific antibodies are mainly operative by eliminating spirochetes from the vector during infestation, the data suggest that Osp A-vaccination for T helper cell immunity alone is not sufficient to prevent Lyme disease.
  • Publication
    Accès libre
    Resolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC
    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.