Efficiency of a myogenic DNA vaccine is strictly dependent upon cellular localization of HIV-1 Pr55(gag).
Most studies on DNA-based immunization have used viral promoters to drive antigen expression. Recently, the use of tissue-specific DNA vaccines has been favored regarding safety issues. In this study, we determined the impact of antigen localization and tissue-specific expression on the induction of humoral as well as cellular immune responses in a BALB/c mouse model. Thereby, we show that using the muscle-specific muscle creatine kinase (MCK) promoter/enhancer the efficiency of immune stimulation is strictly dependent on the ability of HIV-1 Pr55(gag) to be released from cells. By contrast, localization of Pr55(gag) and derivatives thereof plays only a minor role when antigen is constitutively expressed using the ubiquitous viral CMV promoter.
Bojak
Alexandra
A
Institute of Medical Microbiology, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.
Wild
Jens
J
Wolf
Hans
H
Wagner
Ralf
R
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D003402:Creatine Kinase / Q000235:genetics*; D052283:Creatine Kinase, MM Form; D004742:Enhancer Elements, Genetic; D015683:Gene Products, gag / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D005813:Genes, Synthetic; D015750:Genes, gag; D015483:HIV Antibodies / Q000096:biosynthesis; D016655:HIV Core Protein p24 / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007527:Isoenzymes; D011498:Protein Precursors; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D003402:Creatine Kinase; D052283:Creatine Kinase, MM Form