Over the past few years, we completed a series of human trials of recombinant glycoprotein vaccines for treatment and prevention of genital herpes. The vaccines proved inadequate. We turned, therefore, to animal model studies using new classes of HSV vaccines to define ones that appear to be more immunogenic and potentially more effective. We are testing novel DNA-based and live, genetically-engineered vaccines for genital herpes. This has the theoretical advantage of inducing CTL responses. To optimize the responses, we prepared DNA expression cassettes for multiple HSV-2 structure and regulatory genes and lymphocyte co-stimulatory genes. Initial studies in mice using vectors expressing HSV-2 gD have verified that DNA-based vaccines are highly protective against HSV2 infection. The coadministration of vectors for selected HSV regulatory genes did not enhance the activity of gD-expressing vectors. We are now exploring the value of vectors that enhance the copy number of transfected genes in cells, as well as live engineered virus that is deleted for critical genes, rendering the virus avirulent and less able than normal to establish latency or recur.
