The immunogenicity of the tumor-associated antigen α-fetoprotein is enhanced by a fusion with a transmembrane domain

J Biomed Biotechnol. 2012:2012:878657. doi: 10.1155/2012/878657. Epub 2012 Feb 21.

Abstract

Aim: To investigate the ability of recombinant modified vaccinia virus Ankara (rMVA) vector to induce an immune response against a well-tolerated self-antigen.

Methods: rMVA vectors expressing different form of α-fetoprotein (AFP) were produced and characterized. Naïve mice were vaccinated with MVA vectors expressing the AFP antigen in either a secreted, or a membrane-bound, or an intracellular form. The immune response was monitored by an IFNΓ ELISpot assay and antibody detection.

Results: Vaccination with the membrane-associated form of AFP induced a stronger CD8(+) T-cell response compared to the ones obtained with the MVA encoding the secreted or the intracellular forms of AFP. Moreover, the vaccination with the membrane-bound AFP elicited the production of AFP-specific antibodies.

Conclusions: The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chick Embryo
  • Enzyme-Linked Immunospot Assay
  • Interferon-gamma / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Recombinant Fusion Proteins / metabolism
  • Statistics, Nonparametric
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / immunology*
  • alpha-Fetoproteins / metabolism

Substances

  • Membrane Proteins
  • Recombinant Fusion Proteins
  • alpha-Fetoproteins
  • Interferon-gamma