Immunization with a DNA chimeric molecule encoding a hemagglutinin peptide and a scFv CD21-specific antibody fragment induces long-lasting IgM and CTL responses to influenza virus

Vaccine. 2006 Mar 10;24(11):1830-7. doi: 10.1016/j.vaccine.2005.10.029. Epub 2005 Nov 2.

Abstract

Killed viral vaccines are known to induce primarily antibody responses. By contrast DNA vaccination using naked DNA encoding viral antigens induces both humoral and cellular immune responses. Various approaches have been used to construct DNA vaccines with build-in adjuvanticity. We hypothesized that sequences encoding a common epitope of influenza A virus hemagglutinin jointed to sequences encoding a single-chain variable fragment (scFv) antibody fragment to a costimulatory B cell surface receptor would result in the in vivo expression of a chimeric viral peptide with increased immunogenicity. Such a hybrid DNA molecule was constructed by us, encoding a T and B cell epitope-containing influenza hemagglutinin peptide and a scFv antibody fragment binding to mouse complement receptors I and II (CR1 and CR2). A single immunization with a plasmid containing the described construct induced a strong anti-influenza cytotoxic response lasting for more than six months and a weak antibody response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral / blood*
  • Cytotoxicity, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hemagglutination Inhibition Tests
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Immunoglobulin Variable Region / genetics*
  • Influenza A virus / immunology*
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Complement / immunology
  • Receptors, Complement 3d / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccination
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Influenza Vaccines
  • Receptors, Complement
  • Receptors, Complement 3d
  • Vaccines, DNA