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)
Laboratory of Nucleic Acid Vaccines; Department of Medicine, Division of Infectious Diseases and Immunology; Center for Infectious Diseases and Vaccine Research
Animals; Cytotoxicity Tests, Immunologic; Enzyme-Linked Immunospot Assay; Female; HIV-1; Interferon-gamma; Mice; Mice, Inbred BALB C; Protein Transport; T-Lymphocytes; Vaccines, DNA; gag Gene Products, Human Immunodeficiency Virus
Biological Factors | Genetics and Genomics | Immunology and Infectious Disease | Immunology of Infectious Disease | Immunoprophylaxis and Therapy
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.
DOI of Published Version
Hum Vaccin Immunother. 2013 Oct;9(10):2095-102. doi: 10.4161/hv.26009. Epub 2013 Aug 13. Link to article on publisher's site
Human vaccines and immunotherapeutics
Wallace, Aaron; West, Kim; Rothman, Alan L.; Ennis, Francis A.; Lu, Shan; and Wang, Shixia, "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)" (2013). University of Massachusetts Medical School Faculty Publications. 786.