Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes

Woo, Wai-Ping, Doan, Tracy, Herd, Karen A., Netter, Hans-Jurgen and Tindle, Robert W. (2006) Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes. Journal Of Virology, 80 8: 3975-3984. doi:10.1128/JVI.80.8.3975-3984.2006


Author Woo, Wai-Ping
Doan, Tracy
Herd, Karen A.
Netter, Hans-Jurgen
Tindle, Robert W.
Title Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes
Journal name Journal Of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2006-04
Year available 2006
Sub-type Article (original research)
DOI 10.1128/JVI.80.8.3975-3984.2006
Open Access Status DOI
Volume 80
Issue 8
Start page 3975
End page 3984
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society Microbiology
Collection year 2006
Language eng
Subject C1
270303 Virology
730101 Infectious diseases
Abstract Although hepatitis B surface antigen (HBsAg) per se is highly immunogenic, its use as a vector for the delivery of foreign cytotoxic T-lymphocyte (CTL) epitopes has met with little success because of constraints on HBsAg stability and secretion imposed by the insertion of foreign sequence into critical hydrophobic/amphipathic regions. Using a strategy entailing deletion of DNA encoding HBsAg-specific CTL epitopes and replacement with DNA encoding foreign CTL epitopes, we have derived chimeric HBsAg DNA immunogens which elicited effector and memory CTL responses in vitro, and pathogen- and tumor-protective responses in vivo, when the chimeric HBsAg DNAs were used to immunize mice. We further show that HBsAg DNA recombinant for both respiratory syncytial virus and human papillomavirus CTL epitopes elicited simultaneous responses to both pathogens. These data demonstrate the efficacy of HBsAg DNA as a vector for the delivery of disease-relevant protective CTL responses. They also suggest the applicability of the approach of deriving chimeric HBsAg DNA immunogens simultaneously encoding protective CTL epitopes for multiple diseases. The DNAs we tested formed chimeric HBsAg virus-like particles (VLPs). Thus, our results have implications for the development of vaccination strategies using either chimeric HBsAg DNA or VLP vaccines. HBsAg is the globally administered vaccine for hepatitis B virus infection, inviting its usage as a vector for the delivery of immunogens from other diseases.
Keyword Hepatitis B Surface Antigen Vector
T-lymphocyte responses
HBsAg
CTL epitopes for multiple diseases
VLP vaccines
In-vivo
Mammalian-cells
Transgenic Mice
Delta Antigen
Particles
Induction
Q-Index Code C1
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 08:22:32 EST