• English
    • Deutsch
View Item 
  •   OPARU Home
  • Medizinische Fakultät
  • Publikationen
  • View Item
  •   OPARU Home
  • Medizinische Fakultät
  • Publikationen
  • View Item
  • English 
    • English
    • Deutsch
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Stress protein complexed multidomain vaccines identify subdominant CD8 T cells with enhanced anti-viral activity.

Thumbnail
Download
vts_6842_9478.pdf (4.089Mb)
111 Seiten
 
Veröffentlichung
2009-06-05
DOI
10.18725/OPARU-1608
Dissertation


Authors
Wieland, Andreas
Faculties
Medizinische Fakultät
License
Standard (Fassung vom 01.10.2008)
https://oparu.uni-ulm.de/xmlui/license_v2
Abstract
Heat shock proteins (Hsp) of the Hsp70/90 families facilitate cellular immune responses to chaperoned peptides or proteins and have therefore been used as vaccine vehicles. We have developed an expression system in which chimeric proteins with a Hsp-capturing, viral J domain fused to antigen-encoding sequences form stable complexes with eukaryotic stress proteins (Hsp70/73) thus facilitating their expression. In addition to the viral J domain, J domains derived of bacterial and plant origin were able to capture Hsp70/73 and facilitated antigen expression equally well. The tested J domains were also able to bind bacterial Hsp70 (DnaK) thus enabling vaccine production in a large panel of hosts. Purified Hsp/antigen complexes efficiently elicited antigen-specific CD8 T cell responses in mice when delivered as vaccines without adjuvants. The described expression system thus supports the flexible design of multivalent, CD8 T cell-stimulating vaccines. We investigated whether immunodominance hierarchies between CD8 T cell epitopes limit the potential of multivalent, Hsp-binding vaccines. Immunodominance effects were observed analyzing murine H2-Kb-restricted epitopes. Kb/OVA257-264 and Kb/S190-197-specific CD8 T cell responses did not allow priming of a Kb/C93-100-specific CD8 T cell response in mice immunized with multidomain vaccines. However, subdominant Kb/C93-100-specific CD8 T cells were efficiently primed by a HBcAg-encoding vector in 1.4HBV-Smut tg mice (that harbor a replicating HBV genome producing HBV antigens in the liver). Kb/C93-100-specific CD8 T cells accumulated in the liver of vaccinated 1.4HBV-Smut tg mice and suppressed HBV replication. Subdominant epitopes in vaccines can hence prime specific CD8 T cell immunity in a tolerogenic milieu and deliver specific anti-viral effects to HBV-expressing hepatocytes.
Date created
2009
Subject Headings
Hepatitis-B-Virus [GND]
Hitzeschock-Proteine [GND]
Impfung [GND]
MHC Klasse I [GND]
Heat-shock proteins [MeSH]
Keywords
CD8 T Zellen; Immunodominanz
Dewey Decimal Group
DDC 610 / Medicine & health

Metadata
Show full item record

Citation example

Wieland, Andreas (2009): Stress protein complexed multidomain vaccines identify subdominant CD8 T cells with enhanced anti-viral activity.. Open Access Repositorium der Universität Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-1608

Other citation formats



About OPARU | Contact Us
Impressum | Privacy statement
 

 

Advanced Search

Browse

All of OPARUCommunities & CollectionsFacultiesInstitutionsPersonsResource typesUlm SerialsDewey Decimal ClassesFundingThis CollectionFacultiesInstitutionsPersonsResource typesUlm SerialsDewey Decimal ClassesFunding

My Account

LoginRegister

Statistics

View Usage Statistics

About OPARU | Contact Us
Impressum | Privacy statement