Reports for NATAP

AIDS Vaccine 2001 Conference

September 6, 2001 Philadelphia, PA

Closer to AIDS vaccine? 20 prototypes are in trials; researchers feel they'll beat the virus
      Steve Sternberg 09/05/2001 USA Today

Sandra Wearins had to muster all her courage to offer her arms to the nurse preparing to vaccinate her. Wearins, 43, has been terrified of needles all her life, and the needle on the tray wasn't the only thing that scared her.

This was no ordinary vaccine. It contained millions of mutant poxviruses that were packed with genes from the AIDS virus, HIV.

Wearins would get a dose in each arm. Later, she would come back for booster doses. The experimental vaccine, made by Aventis Pasteur, is called ALVAC CP-1452. It is one of the most promising AIDS vaccines now being tested in human volunteers.

It isn't the only one. Nearly 20 prototypes are now in human trials, with more in the pipeline. For the first time in years, the push to find an effective AIDS vaccine is gaining momentum, flush with new projects sponsored by the government, biotech firms, non- profit organizations and the pharmaceutical industry.

All of the experimental vaccines are made of HIV proteins and genes, not whole virus, which is considered too risky. Although most of the prototypes are in the earliest stages of testing, many HIV vaccine researchers are, for the first time in years, confident that they can eventually beat HIV.

Today, many of those researchers, public health experts, drug company representatives and health ministers from hard-hit nations will meet in Philadelphia for AIDS Vaccine 2001, the first in a series of meetings designed to speed vaccines into large-scale trials.

"We have reached a new level of acceleration, not only in what we're doing but in the promise of what can be done," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Even a divided Congress recognizes the importance of developing AIDS vaccines, Fauci will note today in his opening address. Next year, lawmakers will supply $357 million for AIDS vaccine research, a 27% increase over this year's total.

A cast of thousands

If things go as researchers hope, hundreds of thousands of people like Wearins in the USA and abroad will roll up their sleeves for tests that will show whether a vaccine can defeat the deadly virus.

The stakes couldn't be higher. In just two decades, HIV has claimed 22 million lives and now threatens 36 million more, mostly in countries that can't afford expensive treatments. Only priming the immune system to stave off infection -- or, if that doesn't work, to hold the virus in check -- can combat the mushrooming epidemic.

Many clinical-trial volunteers will receive newer vaccines than the version given to Wearins. ALVAC, now in Phase II tests of safety and ability to activate the immune system, soon will be tested for effectiveness. Many other experimental vaccines are now being tested for the first time to see whether they're safe. Volunteering to test an untried vaccine takes a special kind of courage.

"I always think of a hero as an ordinary person in extraordinary circumstances who does what needs to be done," says Mary Allen, a nurse and community liaison for the National Institute of Allergy and Infectious Diseases' (NIAID) HIV Vaccine Trials Network. "I think of our vaccine volunteers like that. They're taking that first bold step of being vaccinated with something that has never been given to humans before."

It is Wearins' job to drum up local volunteers. Wearins, director of community education at the University of Maryland Institute of Human Virology, signed on in February to build support for vaccine trials in Baltimore. A longtime health educator who once fearfully wiped her hands on her skirt after shaking hands with someone who had AIDS -- "I thought, 'My God, can I get AIDS from that?' " -- Wearins now is a veteran AIDS warrior.

Serving on NIH's AIDS vaccine advisory committee led her to get more involved in the development effort. But she had to confront her own fears first. "When I was recruited for this position," she says, "I knew one of the things people would say to me is, 'Well, are you a participant?' How could I ask them to do something I wasn't willing to do?"

As it turned out, the inoculations weren't the most frightening part of the experience. That came the day after Wearins got her first shot, when her immune system reacted to the virus. "I had nausea, chills, fever, anxiety. I'm in bed with the shivers and two blankets over me, and it's probably 85 degrees. I thought, 'Somebody made a mistake and gave me live HIV.'

" Trial supervisor William Blattner reassured her. "That's wonderful," he said. "Your immune system responded really well." In a couple of hours, the scare was over.

Unique risks

HIV vaccine trials pose other unique risks for participants. "You have a vaccine that might cause you to test positive on an HIV test," Allen says.

The stigma of AIDS may taint even vaccine trial participants, says Don Francis, president and co-founder of VaxGen of Brisbane, Calif., whose AIDSVAX is the only one of about 40 vaccines evaluated worldwide that is now in large-scale effectiveness trials. To avoid the risks of disclosure, Francis' team has advised every volunteer in the firm's 5,400 person U.S.-European trial to "choose whom you tell very carefully."

Ever since NIAID began limited AIDS vaccine trials 14 years ago, volunteers have been given photo IDs with a toll-free number in case an insurance company or employer learns of a positive test result and mistakenly believes a volunteer is infected with HIV. Allen or a co-worker checks the messages daily. She says she has never failed to resolve a conflict.

None of the experimental vaccines carry live HIV, researchers say, so infection is impossible. The vaccines now in development contain HIV proteins or genes that produce elements of HIV, but they lack the components that permit HIV to multiply. Sophisticated tests can distinguish between infection and the response to a vaccine.

A motley crew

Volunteers come from all walks of life, says Barney Graham, who runs the vaccine trial unit at NIH. They're paid up to $50 per visit for their time and transportation.

"Some people who participate look at their children and think, 'Can I make this a safer world for them?' Other people have known someone who died of HIV, and though they can't bring that person back to life, they want to do something to protect people in the future," Allen says. "It's a very personal decision."

The vaccines now in the pipeline differ from one another as much as the volunteers who will test them. AIDSVAX is made of purified proteins from HIV's surface. So far, it provokes the immune system to make antibodies, which can keep HIV from infecting cells, but not the potent white blood cells known as killer T-cells that combat infections by purging infected cells from the bloodstream.

AIDSVAX is the only AIDS vaccine now being tested for effectiveness. These trials, in North America, Europe and Thailand, involve about 8,000 volunteers. If two-year results, due out this fall, show that the vaccine protects only 30% of the volunteers, the trial could be halted, and VaxGen could apply for government approval, based on the vaccine's ability to slow the epidemic. If not, the trial will run out its three-year course, and approval will hinge on the final results.

Next comes ALVAC, made by filling a virus, called canarypox, with HIV genes that transform canarypox into a factory for the proteins that make up six components of the AIDS virus.

The researchers use viruses to carry HIV into the bloodstream because they want to provoke a T-cell response, and T-cells are activated only by infected cells such as the mutant canarypox. ALVAC has proved this approach works, producing a bumper crop of killer T-cells. The vaccine currently is undergoing safety tests in the Americas and in Thailand. NIAID and the Department of Defense also have begun gearing up to test ALVAC's effectiveness in people in the USA and Thailand.

Other vaccines now in safety trials are made from DNA that hasn't been injected into viruses, from HIV proteins and from HIV genes packed in a variety of live, but weakened, microbes.

Some vaccines will be tested in tandem, a strategy known as the prime-boost approach. No one knows which of the experimental approaches will work best, singly or together, or if they will work at all, says Susan Buchbinder, director of HIV research for the San Francisco Department of Health and chairwoman of the committee that reviews the all-important effectiveness trials. Only full-scale human trials, Buchbinder says, will provide answers.

"People say mice lie most of the time, monkeys lie some of the time, and people never lie,"she says. "We won't know what works best until we test it in humans."

The website for the Vaccine Conference is:
http://www.AIDSvaccine2001.org