Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1)

Hum Vaccin Immunother. 2013 Oct;9(10):2095-102. doi: 10.4161/hv.26009. Epub 2013 Aug 13.

Abstract

In the current study, immune responses induced by Gag DNA vaccines with different designs were evaluated in Balb/C mice. The results demonstrated that the DNA vaccine with the full length wild type gag gene (Wt-Gag) mainly produced Gag antigens intracellularly and induced a higher level of cell-mediated immune (CMI) responses, as measured by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and cytotoxic T lymphocytes (CTL) assays against a dominant CD8(+) T cell epitope (AMQMLKETI). In contrast, the addition of a tissue plasminogen activator (tPA) leader sequence significantly improved overall Gag protein expression/secretion and Gag-specific antibody responses; however, Gag-specific CMI responses were decreased. The mutation of zinc-finger motif changed Gag protein expression patterns and reduced the ability to generate both CMI and antibody responses against Gag. These findings indicate that the structure and post-translational processing of antigens expressed by DNA vaccines play a critical role in eliciting optimal antibody or CMI responses.

Keywords: DNA vaccine; Gag; HIV-1; antibody; cell mediated immune responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytotoxicity Tests, Immunologic
  • Enzyme-Linked Immunospot Assay
  • Female
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / metabolism*
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Protein Transport
  • T-Lymphocytes / immunology
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology*
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology*
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Vaccines, DNA
  • gag Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma