Document Detail


Optimization of immune responses induced by therapeutic vaccination with cross-reactive antigens in a humanized hepatitis B surface antigen transgenic mouse model.
MedLine Citation:
PMID:  22591777     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The absence of relevant animal models of chronic hepatitis B virus (HBV) infection has hampered the evaluation and development of therapeutic HBV vaccines. In this study, we generated a novel transgenic mouse lineage that expresses human class I and II HLA molecules and the hepatitis B surface antigen (HBsAg). HBsAg and hepatitis B core antigen (HBcAg) administered as plasmid DNAs and recombinant proteins, either alone or in combination, were evaluated as therapeutic vaccine candidates in this mouse model. Our results emphasize the importance of the route of administration in breaking HBsAg tolerance. Although immunizing the transgenic mice with DNA encoding homologous HBsAg was sufficient to induce CD8+ T-cell responses, HBsAg from a heterologous subtype was required to induce a CD4+ T-cell response. Importantly, only prime-boost immunization protocols that combined plasmid DNA injection followed by protein injection induced the production of antibodies against the HBsAg expressed by the transgenic mice.
Authors:
Maryline Bourgine; Sarah Dion; Ophélie Godon; Gerardo Guillen; Marie-Louise Michel; Julio Cesar Aguilar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-14
Journal Detail:
Title:  Virology     Volume:  -     ISSN:  1096-0341     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Institut Pasteur, Laboratoire de Pathogenèse des virus de l'hépatite B, Département de virologie, F-75015 Paris, France; INSERM, U845, Unité de Pathogénèse des hépatites virales B et Immunothérapie, Faculté de Médecine Paris Descartes, F-75015 Paris, France.
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