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).
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.
Laboratory of Nucleic Acid Vaccines; Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
Aaron
A
Wallace
Laboratory of Nucleic Acid Vaccines; Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA; Center for Infectious Diseases and Vaccine Research; University of Massachusetts Medical School; Worcester, MA USA.
Kim
K
West
Center for Infectious Diseases and Vaccine Research; University of Massachusetts Medical School; Worcester, MA USA.
Alan L
AL
Rothman
Center for Infectious Diseases and Vaccine Research; University of Massachusetts Medical School; Worcester, MA USA.
Francis A
FA
Ennis
Laboratory of Nucleic Acid Vaccines; Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
Shan
S
Lu
Laboratory of Nucleic Acid Vaccines; Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
Shixia
S
Wang
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D021381:Protein Transport; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma
DNA vaccine; Gag; HIV-1; antibody; cell mediated immune responses