Nobody dies of Herpesvirus genitalis, but many of the estimated 10percent of the U.S. population it infects regard this painful,embarrassing, recurrent genital inflammation as a living death.
Today, attendees at a conference in Washington on MucosalImmunization, will hear about the latest strategy to build arecombinant vaccine against this sublethal viral scourge.
Immunologist Barbara Araneo, vice president of research atParadigm Biosciences Inc. in Salt Lake City, will report on "VitaminD3-enhanced protection of gD2 nucleic acid vaccine against primaryHerpes Simplex 2 [HSV-2] infection in mice."
Araneo's mice are a female strain specifically bred to model genitalherpes. In the experiment she is reporting, a cohort of these animalsreceived intravaginal injections of one million units of infectiveHSV-2 virions. A week later they got intramuscular shots of theParadigm vaccine, which consists of a plasmid containing the genefor recombinant gD2. This viral surface protein helps the pathogenattach to and penetrate target cells. And it acts as a bull's eye for itshost's immune response.
Mice immunized with the gD2 antigen, Araneo will report, "exhibitedstrong serum and vaginal antibody titers, neutralizing activity inserum . . . mild to moderate clinical symptoms and significantly lowervirus titers over the first 48 hours."
This gD2 antigen also is the target for other ongoing HSV-2 vaccineclinical trials, Paradigm's president and CEO, Martin McGlynn, toldBioWorld Today. "There's a lot of effort in the clinical arena," hesaid, "to make recombinant gD2 and inject it into people. There aretwo big human trials in progress now, one by SmithKline Beecham,the other by Chiron Corp."
Neither, McGlynn pointed out, incorporates two innovations whichmake Paradigm's vaccine uniquely effective:
One is the muscle-cell-specific DNA promoter that drives the gD2antigen.
"The other unique aspect," McGlynn added, "is that we've shown,quite conclusively I think, that the addition of vitamin D3 to the non-viral plasmid vector improves the level of clinical protection in theanimal. It acts as an adjuvant-like immune modulator, boosting theantibody titers that the mice make to gD2, which is novel with anyDNA vaccine.
"We don't have to wait very long to see the animals mount a veryspecific humoral response to the encoded protein. It's really the firstdemonstration of an effective genital herpes vaccine constructed froma nucleic acid vaccine containing an endogenous promoter thatexhibits improved efficacy in the presence of an endogenoushormone [vitamin]."
As for human trials, McGlynn allowed, "To be quite honest, we'relooking to enter into a partnership arrangement with a vaccinedeveloper, because it is not in Paradigm's mandate to develop intothis area specifically. We've already begun talking to a number ofvaccine companies with expertise in this arena, looking to enter into acollaboration that will address that human-trial question amongothers."
Those other questions include the role of killer T cells in protectionand preventing reactivation of the primary infection.
Two immunologists at Utah University School of Medicine, Araneoand immunologist Ray Daynes, founded Paradigm in 1991. They areinventors, McGlynn said, "of a broad range of technologies involvingsteroid hormones, for which the company has a global exclusivelicense."
Infectious diseases specialist John Kriesel, is a co-author on the paperthat Araneo is presenting at the mucosal immunity meeting thismorning. He told BioWorld Today, "In the U.S., the best estimatessuggest that there are half a million new cases of genital herpesdiagnosed per year. Here in Utah, a state with about 2 millionpopulation, the annual incidence is some 3,500."
About 10 percent of the general population in the U.S., Krieseladded, "has recurrent genital herpes symptomatic enough to causethem to seek treatment. And maybe 20 to 40 percent are actuallyinfected, and some of those may be transmitting the virus." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.