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Enhancing t cell activation and antiviral protection by introducing the hiv-1 protein transduction domain into a DNA vaccine

Academic Article
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Overview

authors

  • Leifert, J. A.
  • Lindencrona, J. A.
  • Charo, J.
  • Whitton, J. Lindsay

publication date

  • October 2001

journal

  • Human Gene Therapy  Journal

abstract

  • Protein transduction domains (PTD), which can transport proteins or peptides across biological membranes, have been identified in several proteins of viral, invertebrate, and vertebrate origin. Here, we evaluate the immunological and biological consequences of including PTD in synthetic peptides and in DNA vaccines that contain CD8(+) T cell epitopes from lymphocytic choriomeningitis virus (LCMV). Synthetic PTD-peptides did not induce detectable CD8(+) T cell responses. However, fusion of an open reading frame encoding a PTD to an epitope minigene caused transfected tissue culture cells to stimulate epitope-specific T cells much more effectively. Kinetic studies indicated that the epitope reached the surface of transfected cells more rapidly and that the number of transfected cells needed to stimulate T cell responses was reduced by 35- to 50-fold when compared to cells transfected with a standard minigene plasmid. The mechanism underlying the effect of PTD linkage is not clear, but transit of the PTD-attached epitope from transfected cells to nontransfected cells (cross presentation) seemed to play, at most, a minimal role. Mice immunized once with the plasmid encoding the PTD-linked epitope showed a markedly accelerated CD8(+) T cell response and, unlike mice immunized with a standard plasmid, were completely protected against a normally lethal LCMV challenge administered only 8 days post-immunization.

subject areas

  • Animals
  • CD8-Positive T-Lymphocytes
  • Cell Membrane
  • Cysteine Endopeptidases
  • Cytokines
  • DNA
  • Dose-Response Relationship, Drug
  • Epitopes
  • Genes, MHC Class I
  • HIV-1
  • Lymphocyte Activation
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Multienzyme Complexes
  • Open Reading Frames
  • Peptides
  • Plasmids
  • Proteasome Endopeptidase Complex
  • Protein Structure, Tertiary
  • T-Lymphocytes
  • Time Factors
  • Transfection
  • Vaccines, DNA
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Identity

International Standard Serial Number (ISSN)

  • 1043-0342

Digital Object Identifier (DOI)

  • 10.1089/104303401753153938

PubMed ID

  • 11589830
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Additional Document Info

start page

  • 1881

end page

  • 1892

volume

  • 12

issue

  • 15

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