The FDA has given the green light for the first testing of a DNA-based vaccine in healthy human adults. Within six to eight weeks,researchers at the National Institutes of Allergy and InfectiousDiseases (NIAID) will begin administering Malvern, Pa.-basedApollon Inc.'s prophylactic AIDS vaccine to 16 volunteers in a PhaseI/II clinical trial.

The Phase I/II trial will evaluate whether Apollon's product,Genevax-HIV, can be safely administered to HIV-negativeindividuals and whether it stimulates any measurable immuneresponse over the course of the 18-month study. Ultimately, the goalof a prophylactic AIDS vaccine would be complete protection againstHIV infection.

Apollon launched a Phase I/II trial using the same product as a"therapeutic" vaccine in asymptomatic HIV-infected patients lastJune. (See BioWorld Today, June 19, 1995, p. 1.) That trial markedthe clinical debut of Genevax-HIV, a vaccine based on viral genesrather than the proteins those genes encode. The goal of a so-calledtherapeutic vaccine is to slow or halt disease progression in infectedindividuals. Apollon president and CEO Vincent Zurawski said 15patients have enrolled in the therapeutic vaccine trial with no adverseexperiences reported to date. That trial should be completed by theend of 1996.

The agent currently being tested represents the first component ofApollon's Genevax-HIV prophylactic vaccine program. It consists ofa bacterial plasmid containing two non-infectious HIV genes thatencode the viral envelope (env) glycoproteins, gp 120 and gp 41, plusa third gene, rev, which increases expression of the two env genes.

A second Apollon construct, slated to begin testing later this year,will contain genes encoded by the gag/pol region of the virus (whichincludes the core protein, p24) plus certain enzymatic proteins. Takentogether, these two prophylactic vaccine components could target asmuch as 80 percent of the open reading frame of the HIV genome,theoretically stimulating a broad-based immune response that couldward off infection.

Traditionally, live-attenuated virus vaccines have been used toimmunize patients against viruses, an approach that carriesunacceptable risks in the case of the AIDS virus. "There has recentlybeen a fair amount of reevaluation of the preventive vaccineapproach to combating AIDS because there have been a lot ofattempts to develop one with no clear winner emerging," Zurawskitold BioWorld Today. "Apollon's approach represents a newpotential pathway to solve this problem and these trials could beginto tell us whether that approach has merit."

One of the challenges facing any company developing a preventivevaccine for AIDS is the fact that an effective product will likely causeclinical trial participants to test "positive" for HIV infection.Researchers have fretted over the possible negative consequences ofsuch an outcome in terms of obtaining medical insurance. Zurawskisaid it will be possible using standard confirmatory lab tests todistinguish between individuals who test positive for HIV antibodiesdue to the Genevax-HIV vaccine and those who test positive due toactual HIV infection.

The Genevax-HIV vaccine was developed by Apollon incollaboration with researchers at the University of Pennsylvania andis one of three products covered under a multi-million dollar researchand development pact with Radnor, Pa.-based Wyeth-LederleVaccines and Pediatrics, a business unit of the Wyeth-AyerstDivision of American Home Products. (See BioWorld Today, Oct.27, 1995, p. 1.)

Apollon is a privately-held company that has raised approximately$15 million in equity funding since its inception in 1992. n

-- Lisa Piercey Special To BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.