Design and immunogenicity of a DNA vaccine against primate lentiviruses

A successful vaccine for AIDS must be safe, efficacious, elicit both a cellular and humoral immune response, and be easy to produce and administer. The DNA vaccines described here, pIV and p{dollar}Delta{dollar}IV3, contain a mutated form of the simian immunodeficiency virus (SIV) genome in which a large deletion encompassing the integrase, vif, vpx, and vpr genes has been introduced into the wild type genome. The promoter elements of the 5{dollar}spprime{dollar} long terminal repeat have been replaced with a strong cytomegalovirus promoter. The plasmids produce severely attenuated defective virus particles that are not infectious in vitro. Similar defective virus particles have been shown to be non-pathogenic in Rhesus macaques. The immunogenicity of pIV and p{dollar}Delta{dollar}IV3 was evaluated in rabbits. The constructs are capable of producing both a humoral and cellular immune response that is specific to SIV. Both plasmids elicit a moderate antibody response to the SIV envelope glycoprotein, gp130, in a standard ELISA assay. The humoral response was maintained for several weeks after injection in all animals. Primate lentiviruses attack CD4+ T helper cells that constitute an essential population of the cellular immune system, and the decline of this cell type during infection precedes the manifestation of clinical AIDS. It is therefore important to maintain not only a healthy T cell population, but also one that functions to control and eliminate the infection. Both pIV and p{dollar}Delta{dollar}IV3 promote a strong T cell proliferative response in rabbits to SIV antigens. A response was observed to gp130, gag proteins, and envelope peptides and is sustained for several months after injection. The data presented here clearly show that pIV and p{dollar}Delta{dollar}IV3 fulfill the requirements for a vaccine component against primate lentiviruses. These candidate vaccines are economically and technically easy to produce, and distribution and administration requires no special equipment. They elicit both a humoral and cellular response that endures for several months that is specific to the pathogen. In addition, in contrast to live, attenuated vaccines, the detrimental effects of integration are greatly reduced and reversion to a pathogenic form is unlikely.