Preparation and induction of immune responses by a DNA AIDS vaccine

In an effort to evaluate the feasibility of developing a safe DNA vaccine f or acquired immunodeficiency syndrome (AIDS), we have prepared a plasmid-ba sed immunogen modeled after a naturally occurring noninfectious mutant of t he simian immunodeficiency virus (SIV). The mutant SIV genome produces defe ctive virus particles that are noninfectious in vitro and nonpathogenic in vivo in rhesus macaques. Analysis of the mutant genome revealed a 1.6 kb de letion that is in frame and spans integrase, vif, vpx, and most of vpr and results in a pol/vpr gene fusion. This deletion was introduced into the par ental pathogenic molecular clone and the U3 region of the 5' LTR was replac ed with a cytomegalovirus promoter to produce a candidate DNA vaccine, pIV. After transfection with this plasmid, SIV gag and envelope proteins are ex pressed and properly processed in vitro. When injected into rabbits, PIV el icited an antibody response to SIV gp130 envelope glycoprotein with titers reaching 1:2048, and a strong lymphoproliferative response to SIV gp130 and whole SIV. The potential to produce defective virus particles in vivo with out integrating into the host genome should result in both a strong humoral and cellular immune response in rhesus macaques. In addition, this approac h offers a safe alternative to live attenuated vaccines and DNA vaccines th at are capable of integration.