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.
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.
Qiu
J T
JT
Department of Molecular Microbiology and Immunology, The Johns Hopkins School of Hygiene & Public Health, Baltimore, MD 21205, USA.
Liu
B
B
Tian
C
C
Pavlakis
G N
GN
Yu
X F
XF
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
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