Chicago Tribune - February 5, 2001
Sue Ellen Christian, Tribune Staff Writer

Some vaccines being tested for AIDS try to prevent a virus from infecting the body in the first place. The new strategy acknowledges that infection may be inescapable after exposure, so instead it mobilizes the body's immune system to suppress the disease. It is a seemingly unconventional approach that is fitting for the confounding human immunodeficiency virus, itself hardly a what-you-see-is-what-you-get virus.

The strategy holds the greatest promise for many of the 3,000 scientists gathering this week at the 8th annual Retrovirus Conference. These researchers are pursuing a novel combination strategy that uses two vaccines to attack HIV with a one-two punch.

In the simplest of terms, the combination tactic first uses antibodies to attack the virus, to stop it from infecting the body in the first place -- what would truly be a protective vaccine response. But since HIV is so adept at quickly mutating into different strains, among other elusive qualities, it may escape the antibody attack and infiltrate the body's cells, causing infection.

It is here that the second part of the combination vaccine strategy comes in. A vaccine that mimics the virus creates cellular immunity that is then re-activated when organisms meet the genuine aggressor. The cellular immunity, scientists hope, can sufficiently control the disease to prevent the consequences of full infection. A clinical trial to test the combination vaccine has just begun in the U.S.

Whatever sort of approach ultimately produces the first marketed AIDS vaccine, it probably will not help all people, most scientists believe. While some may be fully protected from the virus, others may experience a far more mild infection because of the vaccine response, and still others may not be helped at all. But, researchers note, every person protected from the disease helps turn the tide on the widespread transmission of infection.

"Everyone was expecting we'd be as successful with AIDS as we were with smallpox," said Dr. Gary Nabel, who is attending the Chicago conference. "But it's clear there is something more with AIDS."

"Even though we might not get to our Holy Grail ... the complete eradication of the virus, we have an excellent chance to turn the tables on the epidemic," Nabel said. For his part, Nabel is embroiled in the AIDS battle as the head of the nation's first Vaccine Research Center, a new, one-of-a-kind facility on the National Institutes of Health campus in Bethesda that has a single mission: Develop an AIDS vaccine.

More than 18 million people have died since the epidemic began, a number that is expected to double over the next decade, according to the Joint United Nations Programme on HIV/AIDS.

Researchers nationwide, whether at Chicago's conference or in labs in Bethesda, would like nothing more than to meet the presidential challenge of developing a successful AIDS vaccine by 2007. Nabel's $30 million center was created to meet that deadline.

There is a quality to the current vaccine research that is unprecedented; an energy and urgency fueled by more funding, innovative research and clinical trials programs, fresh collaborations with private industry, and the ever-mounting global death toll from the disease.

The Chicago conference will only touch on the radical steps under way in the U.S. commitment to discover an AIDS vaccine. The efforts encompass a wide range of players, from top academic researchers hired into government service at the new vaccine center to high-risk women volunteering at the University of Illinois at Chicago in a groundbreaking AIDS vaccine trial. The combination vaccine approach is just one of dozens of strategies being tested in labs, animals and humans as scientists leave no stone unturned in the vaccine search.

"We're nearing a defining moment in AIDS vaccine development that will be in the next five or six years," said Margaret "Peggy" Johnston, assistant director for AIDS vaccine research at the National Institute of Allergy and Infectious Diseases.

"In that time period, we'll either know we're on the right track or able to more accurately predict when we might have a final answer, or we'll be very depressed and know we have to go back to the drawing board."

Scientists know more about the HIV virus than perhaps any other virus ever studied for a vaccine, "It's that we don't know which vaccine works best against it," Johnston said.

HIV has many characteristics that confound efforts to develop a vaccine: The virus mutates at a high rate, it can dodge immune responses by chemically masking its key components and it systematically destroys the so-called "helper T-cells" that help fight infection.

Speaking at the Chicago HIV conference on Sunday, Harvard University researcher Ronald Desrosiers said that while most researchers agree on the need for vaccine development, the challenge is awesome.

"HIV is able to replicate persistently and relentlessly in the face of immune responses," said Desrosiers, a microbiologist who studies how the virus eludes detection by the immune system. "Unfortunately for everyone, the road to a vaccine that's going to be practically effective in the field promises to be a very, very difficult one."

Despite the huge obstacles to making a perfect vaccine, experts said NIAID is trying to mount a newly aggressive strategy of pushing forward vaccine trials rather than waiting for private companies to submit proposals.

More than 60 clinical trials of about 30 possible vaccines are under way worldwide, according to NIAID.

One of the most recent and visible changes in the federal effort to develop an AIDS vaccine is the 50,000-square-foot Vaccine Research Center, a jaunty, contemporary edifice that clings to the edge of the NIH campus. Nabel, 47, has a fourth-floor corner office in which, late last year, diplomas and certificates leaned against the wall awaiting hanging. A white hard hat was stashed on a back shelf. Plucked from the University of Michigan, Nabel has developed novel approaches in gene therapy for AIDS and vaccine strategies against cancer and the Ebola virus.

Eventually, the center will house 100 scientists and support staffers.

As Nabel spoke, the rumble of bulldozers filtered up to his office.

"Our building is dedicated to one goal in its entirety: the development of an AIDS vaccine," he said. "This model is relatively unique; the concept itself is almost an experiment."

A hybrid between the pure research of academia and the biotech industry's emphasis on developing a product, the center will take a vaccine from concept through design through pilot production.

Eventually, the center will work on the development of vaccines for all sorts of diseases, but its immediate mandate is the AIDS vaccine.

"People have been feeling different parts of the elephant with blindfolds on," Nabel said. "I hope the vaccine center becomes a bit of a nerve center to coordinate and interact with other efforts."

Nabel's goal is to have a vaccine being tested in humans within a year of officially opening the center, which will occur later this year.

So far, the only vaccine to make it to a large-scale U.S. clinical trial is funded by the California-based biotech company VaxGen, whose gp120 vaccine develops antibodies to neutralize the HIV virus before it gets into cells.

VaxGen's trial includes 5,400 subjects, including about 100 high-risk women recruited from the streets of Chicago by the University of Illinois at Chicago. No data have emerged from the five-year trial, which is slated to conclude no later than 2003.

Valeta Donahue, 31, of the West Side, is one of the volunteers in the VaxGen trial. The mother of seven enrolled because the trial provides regular free testing for HIV and sexually transmitted diseases. She knows people who have died from AIDS.

"I think the trial is important, very important," she said.

"It could help people and maybe save some lives."

Dr. Richard Novak, associate professor of medicine and infectious diseases at UIC and the principal investigator for the VaxGen trial site in Chicago, said he believes the vaccine "has a reasonable chance of being at least partially effective."

But, he added, the gp120 strategy has a possible downside: The vaccine-induced antibodies that protect against HIV are specific to certain strains of the virus, and as those strains evolve and drift from the versions used to make the vaccine there may be less protection against infection.

Because of the immense cost and scientific resources needed to develop a vaccine, drug companies have not been highly motivated to create AIDS vaccines -- particularly for a largely Third-World market. But with the HIV Vaccine Trials Network formed last year by NIAID, drugmakers can now pass along their vaccine ideas to researchers, who then test the promising concepts in clinical trials funded by the NIAID, for example.

Tribune staff writer Jeremy Manier contributed to this report. E-mail this story to a friend

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