Stakes Are High for VaxGen, AIDS Vaccine

Donald P. Francis is a veteran virus fighter, and HIV has been his most elusive target.

As an epidemiologist for the national Centers for Disease Control and Prevention in the 1970s, he helped eradicate smallpox in Bangladesh, India and Yugoslavia. In Sudan, he cornered Ebola, a deadly virus that causes internal hemorrhaging. Then in the ‘80s at the CDC, Francis was among the first to predict an AIDS epidemic and to attack blood banks for failing to screen donors.

On Monday, Francis, now president of VaxGen Inc. in Brisbane, Calif., will reveal the results of the largest human trial yet of an experimental AIDS vaccine. VaxGen has invested about $100 million in a five-year test of its experimental drug that involved 5,400 people, most of them gay men, in three countries.

The company has closely guarded the long-anticipated results. Trading in VaxGen’s stock on Nasdaq was halted Friday at $13.02, down 21 cents, pending Monday’s announcement.

If the drug is shown to be effective, it could be a turning point in the AIDS epidemic, which has killed nearly 25 million people worldwide in the last two decades. Even a partially effective vaccine could slow the spread of the disease and save lives.

Many scientists doubt that VaxGen’s vaccine will have any effect on the human immunodeficiency virus that causes AIDS. They say the drug is based on a decades-old technology and an outmoded understanding of HIV. The virus -- among the most mutable known to man -- is classified into 11 distinct subtypes, and within those are countless strains. The new drug, called AIDSVAX, targets just two of those strains.

“I would find it amazing if it had any efficacy,” said Caltech President David Baltimore, winner of the Nobel Prize in medicine. “But you don’t know until you test it, and you could make me eat my words.”

Jose G. Esparza, coordinator of the World Health Organization’s AIDS program in Switzerland, said, “The scientific community is divided.... Anyone who tells you the vaccine won’t work is just speculating.”

The stakes are high for VaxGen, an unprofitable biotech company with no licensed products, 115 employees and about seven months of cash remaining.

VaxGen says the results of the trial are secret, known only to the few employees and consultants who worked on the data. They were sequestered while they conducted their review of documents -- including 800,000 case reports -- an unusual step to keep rumors from buffeting the company’s stock.

In the last year VaxGen’s shares have bounced wildly, soaring as high as $23.25 in December, up from $4.81 in June.

The company has plans to raise as much as $150 million by selling more stock, but buyers will be scarce if the vaccine trial results are negative. Some investors appear to be losing confidence: Since April, billionaire Paul Allen has sharply reduced his stake in VaxGen to less than 5% from 17%, and other big shareholders have signaled their intent to sell.

The quest for an AIDS vaccine is littered with setbacks. The most recent came this month when scientists reported that an experimental vaccine from Merck & Co. failed to prevent AIDS in monkeys. And Immune Response, a San Diego company co-founded by late polio vaccine pioneer Jonas Salk, has been struggling for a decade to develop an AIDS vaccine from a dead virus.

But Francis’ effort with AIDSVAX has gone further than any other project. The Food and Drug Administration appears to be willing to approve a vaccine if it works at least 30% of the time, Francis has said. The outlook for a less reliable vaccine isn’t certain. “How low can we go?” Francis asked. “We really don’t know the answer.”

Even if VaxGen’s drug is approved, the vaccine could be a hard sell. Mary Jane Rotheram-Borus, director of UCLA’s HIV prevention research center, said the public is suspicious of vaccines -- witness the uproar over smallpox vaccinations. Some health activists also worry that an AIDS vaccine tested mostly on gay white men would be poorly accepted among blacks and women, groups that account for 60% of new HIV infections.

Skepticism about the VaxGen vaccine is older than the company itself. Francis formed VaxGen in 1995 to license the vaccine from his former employer, Genentech Inc. The biotech giant shelved the product after the National Institutes of Health declined to fund costly human tests. The Genentech version of the vaccine showed mixed results: Some gay men who received it became infected with HIV.

But Francis thought the vaccine could be improved. Genentech licensed its technology, but retained marketing rights to the vaccine and has an 11% stake in VaxGen. Francis persuaded a Genentech scientist, Phillip W. Berman, who developed the vaccine, to join him. Berman, now 54, then redesigned the vaccine to target a second HIV strain.

Within the scientific community, Francis, 60, has long been an outspoken figure on AIDS.

In 1983, Francis was made director of the Centers for Disease Control’s AIDS lab, but he wasn’t content to catalog cases of the disease, then called GRID for gay-related immune disorder. His bosses cringed when he attacked the Red Cross for failing to screen donors. When Francis, a Harvard-trained virologist, condemned bathhouses as sex businesses that spread HIV, gay activists called him a Nazi. But a 1987 book on the early days of the AIDS crisis, “And the Band Played On,” recast Francis as a bold crusader.

Francis joined Genentech in 1992 and quickly teamed up with Berman. In 1989, Berman made a splash with an experiment that showed Genentech’s HIV shots protected chimps from a whopping dose of virus. Within Genentech, the experiment was famous for an added reason: Berman vaccinated the chimps after his boss told him to deep-six the project.

“They are the biotech equivalent of guys in the garage,” said San Francisco hedge fund manager Paul Sonz, an early investor in VaxGen. “Quirky individuals with the right science. That’s how you get innovation.”

Each participant in the VaxGen trial -- 5,100 gay men and 300 women -- received as many as seven shots over three years. Two-thirds were given the vaccine and the rest a placebo. All were HIV negative but had a high risk of getting the virus through sex with infected people.

During the trial, they regularly were tested for HIV infection and answered questions about their sex lives and received counseling on how to avoid the virus. Most participants were Americans, but some lived in Canada and the Netherlands. The firm is conducting a smaller trial of a different AIDS vaccine in Thailand.

For Donald Hicks, 51, who is gay, participating in the trial offered some revenge against a virus that had killed many friends. Hicks said his address book is filled with crossed-off names and telephone numbers.

Hicks, who teaches microbiology at Los Angeles City College, went to a Hollywood clinic for the vaccine. Each time, a nurse swabbed his shoulder with alcohol, then injected a clear fluid beneath his skin. The next day Hicks felt groggy and feverish, as if he was getting the flu.

Midway through the VaxGen trial, a close friend died of AIDS. For weeks, Hicks called his friend’s answering machine to hear his voice. The man’s ashes rest in Hicks’ yard in a memorial surrounded by calla lilies.

As a biologist, Hicks realizes that the vaccine, a genetically engineered copy of a fragment found on HIV, probably can’t protect him completely from AIDS. But he sees it as an important next step in stamping out a disease he studied as a junior scientist in Francis’ lab at CDC. Of his old mentor, Hicks said: “Francis has tremendous intellectual courage. He is just dedicated to getting things done.”

Most vaccines work by stimulating antibodies that snag the virus floating free in the bloodstream. The VaxGen vaccine is designed to work the same way.

In theory, a protein on the surface of HIV is a perfect target for antibodies. But unlike many viruses, HIV has tricks to keep antibodies at bay. When HIV reproduces, it yields strains that antibodies can’t latch onto. HIV also can elude antibodies by shedding its surface protein into the bloodstream.

Research in the field has moved from antibodies to another arm of the immune system. Many scientists believe an effective vaccine must stimulate killer T-cells, which infiltrate and destroy cells infected with HIV. Antibodies don’t recognize HIV once it enters a cell.

VaxGen started with a weakened virus that had been cultivated in a laboratory, a “15-year-old technology,” said John P. Moore, an immunologist at the New York Weill Cornell Medical Center. Antibodies made in response to the VaxGen vaccine are “incredibly weak” and wear off after a year, Moore said.

But Thomas Merigan, director of Stanford University’s AIDS research center, said the vaccine might prevent infection in some people, while slowing the disease in others. “I’d be surprised if they hit a home run, but I wouldn’t be surprised if it showed some efficacy,” he said.

Death rates from AIDS complications have dropped sharply in the developed world, thanks to an arsenal of 16 drugs that help transform the virus into a chronic disease, not just sudden death. Still, there is no cure and the death toll is high in poor countries that lack access to medications.

A partially effective AIDS vaccine, under the correct conditions, can slow the spread of HIV in high-risk groups and save lives, said UCLA biomathematician Sally Blower, an unpaid consultant to VaxGen.

The trouble is that many people associate vaccines with total protection. So once people receive their AIDS shots, they may feel free to engage in riskier sexual behavior and make the epidemic worse.

VaxGen spokesman Lance Ignon dismissed such worries. He said participants in its trial were surveyed about their sexual activity, and risky behavior did not increase overall. But he acknowledged that trial participants received counseling that would be difficult to duplicate in the larger community.

If its vaccine is approved, VaxGen’s first customers probably will be health-care workers willing to pay for even the smallest amount of added protection. VaxGen’s chief executive, Lance K. Gordon, wouldn’t disclose the price, but he observed that hepatitis B vaccine initially cost $100 a person. “We don’t want to be robber barons,” Gordon said.

At Faultline, a gay bar in Hollywood, patrons seem unaware that an AIDS vaccine might be at hand. Owner Shawn Farnsworth said two bartenders volunteered for the VaxGen trial, but few customers have mentioned it since representatives of the company came by years ago to recruit. The buzz drifting around the patio lounge is about medications to control AIDS, not to prevent it.

“They think AIDS is inevitable,” Farnsworth said. “To them, a vaccine is a pipe dream.”