title: Targeting dendritic cells to enhance DNA vaccine potency.
abstract: DNA vaccination that can induce both cellular and humoral immune responses has become an attractive immunization strategy against cancer and infection. Dendritic cells (DCs) play a critical role in the induction of immune responses by DNA vaccination. However, a major problem of DNA vaccination is its limited potency, because only a very limited fraction of injected DNA molecules are taken up by DCS: In this study, we describe a novel DNA vaccination strategy to enhance uptake and presentation of antigens by DCS: Specifically, we developed a DNA vaccine based upon expression of a model hepatitis B virus (HBV) e antigen fused to an IgG Fc fragment. After vaccination, the DNA are taken up by cells that produce and secrete the antigen-Fc fusion proteins. The secreted fusion proteins, in addition to inducing B cells, are efficiently captured and processed by DCs via receptor-mediated endocytosis and then presented to the MHC class II and as -I (cross-priming). The results of this study demonstrate that broad enhancement of antigen-specific CD4+ helper, CD8+ cytotoxic T-cell, and B-cell responses can be achieved by this DNA vaccination strategy. Thus, the strategy capable of inducing all arms of the adaptive immunity may provide a novel, generic design for the development of therapeutic and preventive DNA vaccines.
authors.affiliation: Center for Cell and Gene Therapy, Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: You
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Hester
authors.forename: H C
authors.initials: HC
authors.lastname: Toh
authors.forename: S Y
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D006513:Hepatitis B e Antigens; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA