Abstract
Strategies for inducing an effective immune response following vaccination have focused on targeting antigens to dendritic cells (DCs) through the DC-specific surface molecule DEC-205. The immunogenicity and efficacy of DNA vaccination can also be enhanced by fusing the encoded antigen to single-chain antibodies directed against DEC-205. Here, we investigated this promising approach for its enhancement of hepatitis B virus (HBV)-specific cellular and humoral immune responses and its antiviral effects in HBV transgenic mice. A plasmid DNA vaccine encoding mouse DEC-205 single-chain fragment variable (mDEC-205-scFv) linked with the hepatitis B surface antigen (HBsAg) was constructed. Vaccination with this fusion DNA vaccine in HBV transgenic mice induced robust antiviral T cell and antibody immunity against HBsAg. The levels of serum-circulating HBsAg and the HBV DNA copy number were downregulated by the induction of a higher HBsAg-specific response. Thus, in this study, we demonstrated the therapeutic efficacy of the novel mDEC-205-scFv-fused DNA vaccine in a mouse model of immune-tolerant, chronic HBV infection.
Keywords:
DC-targeting; DNA vaccine; Hepatitis B; Vaccine.
Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology
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Cytokines / immunology
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Cytokines / metabolism
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Enzyme-Linked Immunosorbent Assay
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Female
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Flow Cytometry
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HEK293 Cells
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Hepatitis B / immunology*
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Hepatitis B / prevention & control
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Hepatitis B / virology
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Hepatitis B Surface Antigens / blood
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Hepatitis B Surface Antigens / genetics
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Hepatitis B Surface Antigens / immunology
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Hepatitis B Vaccines / administration & dosage
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Hepatitis B Vaccines / genetics
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Hepatitis B Vaccines / immunology*
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Hepatitis B virus / genetics
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Hepatitis B virus / immunology*
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Hepatitis B virus / physiology
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Humans
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Immunity, Humoral / immunology*
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Mice, Inbred BALB C
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Mice, Transgenic
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Minor Histocompatibility Antigens
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Single-Chain Antibodies / genetics
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Single-Chain Antibodies / immunology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Vaccination / methods
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
Substances
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Antigens, CD
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Cytokines
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DEC-205 receptor
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Hepatitis B Surface Antigens
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Hepatitis B Vaccines
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Lectins, C-Type
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Minor Histocompatibility Antigens
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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Single-Chain Antibodies
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Vaccines, DNA