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Gern, Lise
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Gern, Lise
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- PublicationAccès libreT helper cell priming of mice to Borrelia burgdorferi Osp A leads to induction of protective antibodies following experimental but not tickborne infection
;Zhong, Weimin; ;Kramer, Michael ;Wallich, ReinhardSimon, Markus MAntibodies 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. - PublicationAccès libreResolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC
;Zhong, Weimin; ;Stehle, Thomas ;Museteanu, Crisan ;Kramer, Michael ;Wallich, ReinhardSimon, Markus MVaccination 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.