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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
    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.