Abstract
In an effort to evaluate the feasibility of developing a safe DNA vaccine for acquired immunodeficiency syndrome (AIDS), we have prepared a plasmid-based immunogen modeled after a naturally occurring noninfectious mutant of the simian immunodeficiency virus (SIV). The mutant SIV genome produces defective virus particles that are noninfectious in vitro and nonpathogenic in vivo in rhesus macaques. Analysis of the mutant genome revealed a 1.6 kb deletion 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 parental pathogenic molecular clone and the U3 region of the 5' LTR was replaced with a cytomegalovirus promoter to produce a candidate DNA vaccine, pIV. After transfection with this plasmid, SIV gag and envelope proteins are expressed and properly processed in vitro. When injected into rabbits, pIV elicited 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 without integrating into the host genome should result in both a strong humoral and cellular immune response in rhesus macaques. In addition, this approach offers a safe alternative to live attenuated vaccines and DNA vaccines that are capable of integration.
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