Old but interesting
Don Hildebrand was just a few months into his retirement when he got the call from Rafi Ahmed, director of the Emory Vaccine Center.
Although Hildebrand, a 30-year veteran of the biopharmaceutical industry, was looking forward to reuniting with his hobbies and playing the stock market from his home in Athens, he was about to get pulled back into the business.
New technology developed by Emory scientist Harriet Robinson had protected 22 out of 23 monkeys from developing AIDS, and Ahmed wanted Hildebrand to help create GeoVax, a company to develop, manufacture and commercialize the potential vaccine.
Hildebrand agreed, and six years later he’s working out of a series of modular labs sequestered on Emory’s Briarcliff Campus. The yellow paneled buildings — filled with laboratory equipment, machinery, pipette tips and latex gloves — are a far cry from the high-powered corporate environment he used to inhabit. But some Emory officials and scientists say GeoVax is the world’s best hope for defeating the deadly AIDS virus.
The tiny company has yet to make any money — as of Sept. 30 it had lost more than $3 million this year due to increasing costs and zero cash flow — and it faces stiff competition from global pharmaceutical organizations like Eurovac and Merck. But Emory, which put up $750,000 to help create the company and owns $39.78 million in GeoVax stock, has pinned its hopes on Robinson’s unique approach to developing an AIDS vaccine.
The technology utilizes a dual-pronged approach to identify and then defend against AIDS, which is notoriously difficult to stop because the virus constantly mutates. GeoVax’s efforts were rewarded with a $15 million grant from the National Institutes of Health in September.
The first phase of human testing, started in 2004, proved the potential vaccine was safe for use, and the company hopes to begin the second phase in clinical trials with widespread tests during the middle of next year.
The Dynamic Duo
GeoVax’s scientific successes are a result of a close collaboration between Hildebrand and Robinson.
Robinson praises Hildebrand’s business savvy, crediting him with making the most of GeoVax’s relatively small budget.
“I have never seen someone squeeze as much value out of a nickel as he is able to do,” Robinson said. “If the vaccine becomes a reality, which we intend it to become, it will be due as much to his business skills as our having started a good product through the pipeline.”
Hildebrand, a gregarious, heavyset man, has always had an eye for turning a profit. As an undergraduate at the University of Wisconsin-Madison, he and a classmate imported and sold Sri Lankan batik paintings to make a few bucks on the side.
About 12 people, mostly scientists, work at GeoVax directly, with several individuals working at other locations. Contractors around the world are hired to manufacture the vaccine.
After four years, GeoVax entered a reverse merger with Dauphin Technology Inc., making it a public company and opening it up to receive further investment. In the last six years, Hildebrand said, the company has received at least $50 million in private investments and grant money. Emory remains the largest shareholder, owning slightly more than 30 percent of GeoVax.
Hildebrand admits a larger budget would help push development and testing at a faster pace. But like others at Emory, he has placed his faith in Robinson’s technology, which lies at the heart of GeoVax’s mission.
“Working with Dr. Robinson is absolutely fabulous as she is an extremely wonderful person, exceptionally talented and a true pleasure to work with,” Hildebrand said.
Most HIV vaccines involve vaccine vectors. A vaccine vector is a weakened version of a virus that carries a protein recognized by the body as foreign, from a disease-causing agent.
The vector delivers the protein to the body and stimulates the immune system to act, “fooling” it into generating an immune response against the foreign protein.
But GeoVax takes another approach. The base technology for the vaccine, a DNA/MVA combination currently under patent review, was developed by Robinson and is different from competitors because it utilizes broad immune responses to combat multiple HIV proteins — the same concept that is behind multidrug therapy.
“It is much harder to escape three drugs than one — similarly, it is much harder to escape a multi-target immune response,” Robinson said.
Two virus types compose the vaccination. The DNA part works by injecting viral genes into healthy cells. This boosts the immune response against individual parts of the virus. Then, upon infection, these antibodies are more likely to recognize and destroy the virus, even if some viral genes have gained mutations.
Then the MVA component, which is a modified smallpox virus, creates a focused immune response to HIV. Although the vaccine would not prevent a HIV infection, it would prevent the development of AIDS and the destruction of the immune system.
Robinson was recruited by Emory from the University of Massachusetts School of Medicine and took up a position as the chief of the Division of Microbiology and Immunology at Yerkes National Primate Research Center in 1998.
By the time she arrived at Emory, the vaccine had been subjected to more than 15 years of trials in non-human primates. These trials revealed that the vaccine stimulated the right kind of immune responses that would protect against the development of AIDS when a person is infected with the HIV virus, Hildebrand said.
Staying One Step Ahead
At the HIV Vaccine Trials Network (HVTN) meetings in Seattle in early November, it was announced that a potential vaccine produced by Merck had failed in ongoing trials in the United States and Africa. More people developed HIV in the vaccine group compared to the placebo group.
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in a statement on the NIAID website that the new analyses were “disappointing and puzzling” and that “failure of this HIV vaccine product was unexpected.”
Merck Public Affairs Director Nalini Saligram said the vaccine was clearly not working, a “disappointing finding.” Because no live HIV virus was used in making the vaccine, she said the vaccine itself could not have caused HIV.
“We are wondering whether [the results were] due to chance, due to the vaccine itself, or due to some biological phenomenon we do not quite understand yet,” Saligram said.
The recent vaccine setback did not affect the GeoVax vaccine, based on a different technology.
“GeoVax AIDS vaccines showed better protection in the non-human primate models than anybody else. That protection is likely to carry over to humans,” Hildebrand said. “That is something the other vaccine companies have not been able to develop or prove.”
GeoVax also believes it may be able to help treat as well as prevent AIDS. Preliminary work is being performed by Emory scientist Rama Amara on monkeys already infected with the AIDS virus but still have intact immune systems.
The monkeys are put on drug treatment programs using the GeoVax vaccine to reduce the virus level in the body of individuals, then vaccinated with the GeoVax DNA and MVA vaccines and taken off the drug program.
Drug treatment programs have severe negative side effects and can cost from $15,000 to $75,000 per year, a significant hurdle for developing countries and many patients in the U.S.
“If we can develop a program where we can vaccinate people already infected with the virus but still have an intact immune system, we may have a way to economically protect these people
