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Immunization with the gene expressing woodchuck hepatitis virus nucleocapsid protein fused to cytotoxic-T-lymphocyte-associated antigen 4 leads to enhanced specific immune responses in mice and woodchucks

Academic Article
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Overview

authors

  • Lu, M.
  • Isogawa, Masanori
  • Xu, Y.
  • Hilken, G.

publication date

  • May 2005

journal

  • Journal of Virology  Journal

abstract

  • A number of options are available to modify and improve DNA vaccines. An interesting approach to improve DNA vaccines is to fuse bioactive domains, like cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), to an antigen. Such fusion antigens are expressed in vivo and directed to immune cells by the specific bioactive domain and therefore possess great potential to induce and modulate antigen-specific immune responses. In the present study, we tested this new approach for immunomodulation against hepadnavirus infection in the woodchuck model. Plasmids expressing the nucleocapsid protein (WHcAg) and e antigen (WHeAg) of woodchuck hepatitis virus (WHV) alone or in fusion to the extracellular domain of woodchuck CTLA-4 and CD28 were constructed. Immunizations of mice with plasmids expressing WHcAg or WHeAg led to a specific immunoglobulin G2a (IgG2a)-dominant antibody response. In contrast, fusions of WHcAg to CTLA-4 and CD28 induced a specific antibody response with comparable levels of IgG1 and IgG2a. Furthermore, the specific IgG1 response to WHcAg/WHeAg developed immediately after a single immunization with the CTLA-4-WHcAg fusion. Woodchucks were immunized with plasmids expressing WHeAg or the CTLA-4-WHcAg fusion and subsequently challenged with WHV. CTLA-4-WHcAg showed an improved efficacy in induction of protective immune responses to WHV. In particular, the anti-WHsAg antibody response developed earlier after challenge in woodchucks that received immunizations with CTLA-4-WHcAg, consistent with the hypothesis that anti-WHs response is dependent on a Th cell response to WHcAg. In conclusion, the use of fusion genes represents a generally applicable strategy to improve DNA vaccination.

subject areas

  • Animals
  • Antibody Specificity
  • Antigens, CD
  • Antigens, CD28
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Drug Evaluation, Preclinical
  • Hepatitis B
  • Hepatitis B Antibodies
  • Hepatitis B Vaccines
  • Hepatitis B Virus, Woodchuck
  • Hepatitis, Viral, Animal
  • Immunoglobulin G
  • Injections, Intramuscular
  • Marmota
  • Mice
  • Mice, Inbred BALB C
  • Nucleocapsid
  • Nucleocapsid Proteins
  • Plasmids
  • Vaccination
  • Vaccines, DNA
  • Vaccines, Synthetic
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Identity

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.79.10.6368-6376.2005

PubMed ID

  • 15858020
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Additional Document Info

start page

  • 6368

end page

  • 6376

volume

  • 79

issue

  • 10

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