Use of novel insertion sites for the development of polyvalent ORFV D1701-V vectored vaccines

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dc.contributor.advisor Rammensee, Hans-Georg (Prof. Dr.) Salomon, Ferdinand 2019-12-17T11:11:38Z 2019-12-17T11:11:38Z 2021-12-11
dc.identifier.uri de_DE
dc.description.abstract Viral vector-based vaccines are promising to elicit strong cellular and humoral immune responses. Within the genus Parapoxvirus of the Poxviridae, the Orf Virus (ORFV) strain D1701-V comprises various properties particularly favorable for the development of a vector platform technology and was shown to facilitate various vaccination approaches. To enhance viral vectors’ immunogenicity, current strategies implement the use of immunomodulatory elements and the elimination of viral immunomodulatory genes still present in the viral genome. To allow the insertion of multiple transgenes into a single vector, the present work examines the suitability of novel insertion sites for transgene expression by simultaneous deletion of ORFV D1701-V encoded genes non-essential for viral replication. Novel D1701-V deletion mutants were subjected to detailed characterization of the genetic stability of inserted transgenes, their growth behavior and capability to induce transgene expression in different target cells in vitro. Additionally, the D1701-V mutants’ immunogenicity was analyzed by their ability to activate pro-inflammatory pathways, peripheral blood mononuclear and antigen presenting cells, or to induce antigen-specific immune responses in vitro and in vivo. Additionally, proof-of-concept studies were performed to evaluate the suitability of ORFV D1701-V recombinants for the expression of immune checkpoint inhibitors (ICIs). en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.classification Impfstoff de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.ddc 610 de_DE
dc.title Use of novel insertion sites for the development of polyvalent ORFV D1701-V vectored vaccines en
dc.type PhDThesis de_DE
dcterms.dateAccepted 2019-12-11
utue.publikation.fachbereich Biologie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE
utue.publikation.noppn yes de_DE


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