Dokument: Vaccine development against gamma herpesvirus infection in a murine surrogate model
Titel: | Vaccine development against gamma herpesvirus infection in a murine surrogate model | |||||||
URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=41107 | |||||||
URN (NBN): | urn:nbn:de:hbz:061-20170207-131435-4 | |||||||
Kollektion: | Dissertationen | |||||||
Sprache: | Englisch | |||||||
Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
Medientyp: | Text | |||||||
Autor: | Dr Samreen, Baila [Autor] | |||||||
Dateien: |
| |||||||
Beitragende: | Prof. Dr. Drexler, Ingo [Betreuer/Doktorvater] Prof. Dr. Feldbrügge, Michael [Gutachter] | |||||||
Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
Beschreibung: | Gamma herpesviruses are known to establish a lifelong persistent infection in association with a number of malignancies in the immunosuppressed host. A mouse model of gamma herpesvirus (MHV68) has been utilized to elucidate the immune response of gamma herpesvirus infection, having genetic similarities with human lymphocrypto- (e.g EBV) and rhadinoviruses (e.g KSHV). During infection, gamma herpesviruses undergo a lytic infection cycle for 7 to 12 days and establish latent infection after 13 to 42 days. Moreover, the latent virus may reactivate due to immune suppression in transplant patients likewise in AIDS patients. Innate immunity is activated by, but fails to control the viral infection. Generally, adaptive T-cells play an important role in initially controlling the acute infection and subsequently maintaining the viral infection in a latent state. However, the nature of the T-cell response and specific viral epitopes eliciting protective immune responses are poorly understood. During infection, gamma herpesviruses undergo a lytic and latent phase of infection and express distinct antigens in each phase. We have used recombinant vaccines to analyze the adaptive immune response upon MHV68 infection, in particular CD4+ and CD8+ T-cells involved in the lytic, latent and reactivation phase, respectively. Particularly, recombinant modified vaccinia virus Ankara (rec-MVA) are widely used for antigen delivery in clinical research for its high level of gene expression and immunogenicity. Therefore, we have generated rec-MVA vaccines encoding MHC class I and II-restricted epitopes of MHV68 by using MVA-BAC homologous recombination technology. We have established antigen-specific cytotoxic T cell lines against MHV68 antigens, which specifically recognized exo and endogenously presented peptide ligands. We have found strong immune responses induced by rec-MVA vaccines for MHC-class I/II-restricted epitopes of MHV68 in immunized mice during the acute and memory phase after single or prime/boost vaccinations. In addition, the protective capacity of prophylactic rec-MVA vaccination against a challenge with MHV68 has beenshown in the acute and latent phase of infection. Briefly, all of this information will augment the advancement of vaccine development against the herpes virus infection. | |||||||
Lizenz: | Urheberrechtsschutz | |||||||
Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Virologie | |||||||
Dokument erstellt am: | 07.02.2017 | |||||||
Dateien geändert am: | 07.02.2017 | |||||||
Promotionsantrag am: | 16.12.2016 | |||||||
Datum der Promotion: | 31.01.2017 |