title: A retroviral DNA vaccine vector.
abstract: A versatile DNA vaccine (pdIV3) was constructed by replacing the integrase, vif, vpx, and vpr genes of a pathogenic simian immunodeficiency virus (SIV) molecular clone with a linker containing unique cloning sites. The 5' long terminal repeat (LTR) is truncated and transcription is controlled by a cytomegalovirus (CMV) promoter. The construct expresses Gag and Env in vitro and noninfectious virus particles are produced from transfected cells. The ability of pdIV3 to promote cellular and humoral immune responses, along with the flexibility of the linker design to allow insertion of immunostimulatory genes in future constructs, makes this a useful base vector for immunization against primate lentiviruses. We present the construction of a retroviral plasmid designed to serve as a template for the development of safe and effective vaccines against primate immunodeficiency retroviruses. This vaccine component should facilitate the simultaneous induction of cellular and humoral immune responses that protect primates against infection with SIV and human immunodeficiency virus (HIV) and the development of acquired immune deficiency syndrome (AIDS). This plasmid could induce the appropriate immune response required to attack both cell-free and cell-associated viruses. The lack of infectivity, the inability to integrate, and the SIV origin make this construct a safe alternative to attenuated vaccines based on HIV. In addition, we intend to develop this construct as an immunotherapeutic approach to lower the viremia in AIDS patients.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis 95616, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: J V
authors.initials: JV
authors.lastname: Torres
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D019556:COS Cells; D002522:Chlorocebus aethiops; D003673:Defective Viruses / Q000276:immunology* / Q000302:isolation & purification; D016346:Gene Products, vif / Q000172:deficiency / Q000235:genetics; D005822:Genetic Vectors / Q000276:immunology*; D019426:Integrases / Q000172:deficiency / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D010957:Plasmids; D011817:Rabbits; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019444:Vaccines, DNA / Q000276:immunology*; D054334:Viral Regulatory and Accessory Proteins / Q000172:deficiency / Q000235:genetics; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016346:Gene Products, vif; C074286:VPX protein, Human immunodeficiency virus 2; C513059:VPX protein, Simian immunodeficiency virus; D019444:Vaccines, DNA; D054334:Viral Regulatory and Accessory Proteins; D014765:Viral Vaccines; D019426:Integrases