title: Enhancement of primary and secondary cellular immune responses against human immunodeficiency virus type 1 gag by using DNA expression vectors that target Gag antigen to the secretory pathway.
abstract: In this study, we have investigated the influence of antigen targeting after DNA vaccination upon the induction of cellular immune responses against human immunodeficiency virus type 1 (HIV-1) Gag. In addition to the standard version of HIV-1 Gag, we constructed Gag expression vectors that encode a secreted (Sc-Gag) and a cytoplasmic (Cy-Gag) Gag molecule. Although all three HIV-1 Gag expression vectors induced detectable humoral and cellular immune responses, after intramuscular injection the DNA vector encoding the Sc-Gag generated the highest primary cytotoxic T-lymphocyte (CTL) and T-helper responses. Mice immunized with one of the HIV-1 Gag DNA vectors (but not with the control vector pcDNA3. 1) developed a protective immune response against infection with recombinant vaccinia virus expressing HIV-1 Gag, and this response persisted for 125 days. The magnitude of the protection correlated with the levels of Gag-specific ex vivo CTL activity and the number of CD8(+) T cells producing gamma interferon. The DNA vector encoding the Sc-Gag induced higher levels of protection and greater secondary CTL responses than did the DNA vector encoding Cy-Gag.
authors.affiliation: Department of Molecular Microbiology and Immunology, The Johns Hopkins School of Hygiene & Public Health, Baltimore, MD 21205, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Qiu
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Tian
authors.forename: G N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: X F
authors.initials: XF
authors.lastname: Yu
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D002455:Cell Division; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007424:Intracellular Fluid / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010053:Ovary / Q000821:virology; D013194:Staining and Labeling / Q000379:methods; D013601:T-Lymphocytes / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D036022:Capsid Proteins; D015683:Gene Products, gag; C071884:NCP7 protein, Human immunodeficiency virus 1; D019444:Vaccines, DNA; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D015847:Interleukin-4; D007371:Interferon-gamma