Manipulation of pathogen-derived genes to influence antigen presentation via DNA vaccines

Vaccine. 1999 Aug 6;17(23-24):3030-8. doi: 10.1016/s0264-410x(99)00171-1.

Abstract

To gain insight into the routes of presentation of pathogen sequences via DNA vaccines, we have compared the abilities of sequences encoding fragment C of tetanus toxin (FrC) and influenza A virus nucleoprotein (NP) to induce antibody or cytotoxic T-cell (CTL) responses in vivo. Strong antibody and CTL responses were induced against FrC targeted to the endoplasmic reticulum (ER) and both were reduced by removal of the leader sequence. In contrast, targeting of NP to the ER generated only a modest antibody response, likely due to misfolding in this site. Removal of the leader sequence led to anti-NP antibodies via cross-priming. For NP, induction of CTLs was not influenced by the leader sequence. Exogenous FrC or NP delivered as proteins were unable to induce CTLs. Routes to induction of optimal immune responses via DNA evidently differ according to the nature of the encoded pathogen sequence. Understanding processing pathways for pathogen sequences should assist rational design of DNA vaccines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / blood
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / blood
  • Antigen Presentation / genetics*
  • COS Cells
  • Cytotoxicity, Immunologic / genetics
  • Influenza A virus / genetics
  • Influenza A virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nucleocapsid Proteins
  • Nucleoproteins / genetics*
  • Nucleoproteins / immunology*
  • Peptide Fragments / genetics*
  • Peptide Fragments / immunology*
  • Protein Sorting Signals / genetics
  • RNA-Binding Proteins*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / microbiology
  • T-Lymphocytes, Cytotoxic / virology
  • Tetanus Toxin / genetics*
  • Tetanus Toxin / immunology*
  • Transfection
  • Vaccines, DNA / genetics*
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Core Proteins / genetics*
  • Viral Core Proteins / immunology*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology

Substances

  • Antibodies, Bacterial
  • Antibodies, Viral
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • Nucleoproteins
  • Peptide Fragments
  • Protein Sorting Signals
  • RNA-Binding Proteins
  • Tetanus Toxin
  • Vaccines, DNA
  • Vaccines, Synthetic
  • Viral Core Proteins
  • Viral Vaccines
  • tetanus toxin fragment C