ABSTRACT
A means of inducing gene expression by simultaneous infection with three recombinant adenoviruses (Ad) is described. The simian immunodeficiency virus (SIV) envelope-coding region was placed under the control of the human immunodeficiency virus type 1 (HIV-1) Tat and Rev proteins provided in trans by distinct Ad vectors (Ad-tat; Ad-rev). Coinfection of cells with the three recombinant adenoviruses led to induction of high levels of SIV env mRNA and protein synthesis, while inoculation of mice elicited anti-Env antibodies. Insertion of the poliovirus VP1 neutralization epitope (C3) in the V1 hypervariable region of SIV envelope not only proved to be highly immunogenic for the poliovirus epitope but also enhanced the kinetics of anti-SIV Env antibody production. By contrast, insertion in V4 elicited no anti-C3 response and only normal anti-Env responses.
Subject(s)
B-Lymphocytes/immunology , Gene Products, env/immunology , Gene Products, rev/immunology , Gene Products, tat/immunology , Poliovirus/immunology , Simian Immunodeficiency Virus/enzymology , Vaccines, Synthetic , Viral Vaccines , Adenoviridae , Amino Acid Sequence , Animals , Antibody Formation , Base Sequence , DNA Primers , Genetic Variation , HIV-1/genetics , Humans , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Recombinant Fusion Proteins , Simian Immunodeficiency Virus/genetics , rev Gene Products, Human Immunodeficiency Virus , tat Gene Products, Human Immunodeficiency VirusABSTRACT
Over the past 15 years, advances in molecular biology have permitted in vitro and in vivo gene transfer into mammalian cells. Genetically engineered microorganisms are highly promising developments for gene therapy and the future of vaccines. Such vectors constitute genuine tools for high level expression of heterologous genes for both therapeutic and induced immunity applications. Several vector systems have emerged with different relative advantages and limits depending on the proposed application. Adenovirus (Ad) has gained our interest, and in this review we focus on its applicability as a vaccine vector. We describe its potentials, as well as some of the foreseen obstacles related essentially to its use in preventive medicine.
