@phdthesis{Ziegler2011,
  author    = {Ziegler, Birgit},
  title     = {Impfverhalten bei Fr{\"u}hgeborenen mit einem Geburtsgewicht unter 1500 Gramm - eine deutschlandweite Erhebung im Alter von 2 Jahren},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64818},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Fr{\"u}hgeborene Kinder haben ein erh{\"o}htes Risiko f{\"u}r impfpr{\"a}ventable Erkrankungen. Von der STIKO wird explizit empfohlen, sehr und extrem Fr{\"u}hgeborene fr{\"u}hzeitig nach ihrem chronologischen Alter, also nach dem gleichen Impfplan, der auch f{\"u}r Reifgeborene gilt, zu impfen. Studien aus den USA oder der Schweiz konnten zeigen, dass Impfungen bei dieser Risikopopulation h{\"a}ufig versp{\"a}tet durchgef{\"u}hrt werden. F{\"u}r Deutschland gab es hierf{\"u}r bisher keine Daten. In der hier vorliegenden Pilotstudie wird das Impfverhalten bei 332 extrem und sehr Fr{\"u}hgeborenen deutschlandweit im Alter von mind. 2 Jahren analysiert. Die Grundimmunisierungen mit dem 5 - bzw. 6-fach Impfstoff sowie mit dem Pneumokokkenimpfstoff wurden konsequent durchgef{\"u}hrt, w{\"a}hrend die Auffrischimpfungen im 2. Lebensjahr deutlich seltener erfolgten. Ein {\"a}hnliches Impfverhalten zeigte sich auch bei den MMR(V)-Impfungen mit einer deutlich verminderten Compliance bei der Auffrischimpfung. Nur bei einem der 332 erfassten Kinder kam es zu einer schweren Nebenwirkung mit Bradykardie und Abfall der Sauerstoffs{\"a}ttigung. Insgesamt zeigte sich v.a. ein Defizit bei der Durchf{\"u}hrung der Auffrischimpfungen und bei der rechtzeitigen Applikation der Impfungen bei diesem speziellen Risikokollektiv.},
  subject      = {mpfungen bei extrem und sehr fr{\"u}h Geborenen},
  language  = {de}
}
@phdthesis{Bach2007,
  author    = {Bach, Patricia},
  title     = {Immunogenicity of antigen-displaying virus-like particles and their use as a potential vaccine against prion diseases},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25889},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of infectious neurodegenerative diseases that are associated with misfolding of the cellular form of the cellular prion protein (PrPC) into a disease associated conformer (PrPSc). No therapy for prion diseases is available at present. So far, anti-PrPC vaccination is hampered by immunological tolerance of the mammalian immune system to endogenous PrPC. The aim of this thesis was to set up a new vaccination strategy based on virus-like particles (VLP) to induce anti-PrPC antibody responses in PrPC-competent mice. In a first step it was assessed whether VLP have the capacity to induce antibody responses that are protective against conventional pathogens. For this purpose, VLP displaying the vesicular stomatitis virus-gylcoprotein (VLP-VSV) were generated and tested for their immunogenicity. Similarly to live vesicular stomatitis virus (VSV), replication deficient VLP-VSV induced T help-independent VSV neutralizing IgM responses that switched to the IgG subclass in a T help-dependent manner. Furthermore, type I IFN receptor (IFNAR) triggering only marginally affected VLP-VSV induced neutralizing IgM responses, whereas it was critically required to promote the IgG switch. The analysis of conditional knockout mice with a lymphocyte-specific IFNAR deletion revealed that IFNAR triggering of lymphocytes did not play a crucial role, neither upon VLP-VSV nor VSV immunization. Collectively, these data verified the high immunogenicity of VLP. Therefore, in a next step VLP were generated displaying the C-terminal half of PrP (residues 121-231aa) fused to the platelet derived growth factor receptor (PDGFR) transmembrane region (VLP-PrPD111) for anti-PrPC immunization. On the surface of such retroparticles, PrPC was expressed at high levels as determined by electron microscopy. VLP-PrPD111 immunization of Prnp-deficient (Prnp0/0) mice resulted in antibody response specifically binding the cellular form of PrPC. Upon intravenous injection of wild-type mice, high PrPC-specific IgM responses were induced, whereas the T cell-dependent switch from the IgM to the IgG subclass was less pronounced. As a consequence, anti-PrPC titers were rather short-lived. The impaired subclass switch was probably related with host T cell tolerance to endogenous PrPC. Attempts to increase anti-PrPC IgG responses in wild-type mice via administration of VLP-PrPD111 emulsified in various different adjuvants failed. Nevertheless, in single individuals low IgG antibodies were induced after immunization of VLP-PrPD111 emulsified in CFA. To circumvent T cell tolerance in wild-type mice, a multitude of different immunization strategies was tested, including priming and boosting protocols with different types of VLP or VLP expressing PrPC together with foreign T helper epitopes. Overall, those efforts did not improve anti-PrPC IgG responses in wild-type mice. Interestingly, anti-PrPC antibodies induced in Prnp0/0 mice reduced PrPSc levels in prion infected cell cultures, whereas serum of vaccinated wild-type mice did not. To assess the protective capacity of VLP-PrPD111 induced immune responses, vaccinated wild-type mice were infected with scrapie (RML 5.0). Unfortunately, vaccinated mice did not show a significant delay in the onset of scrapie. In a last part of the thesis it was studied whether in the absence of T cell help activated "memory" B cells were able to produce anti-PrPC specific antibodies. To address this question, PrPC-specific memory B cells were sorted from vaccinated Prnp0/0 mice and adoptively transferred into wild-type recipient mice. Upon VLP-PrPD111 challenge, no PrPC-specific IgG titers were induced in the recipients. Nevertheless, several VLP-PrPD111 challenged recipient mice were protected against scrapie infection. In conclusion, VLP were characterized as highly immunogenic vaccines that were used to elucidate various questions concerning adaptive immune response and basic mechanisms of PrPC-specific tolerance vs. immunity. Remarkably, VLP-PrPD111 was able to induce native PrPC-specific antibodies in wild-type mice but major difficulties associated with PrPC-specific tolerance made efficacious scrapie vaccination impossible. New vaccination approaches are being tested to overcome these limitations.},
  subject      = {Prion},
  language  = {en}
}