HIV vaccine is best hope in 20 years

An international effort coordinated by Seattle scientists will soon begin testing the most promising AIDS vaccine in more than 20 years of research.

In smaller trials, the vaccine has produced the strongest immune response ever against the AIDS virus, said Dr. Larry Corey, lead scientist for the international HIV Vaccine Trials Network, based at the Fred Hutchinson Cancer Research Center in Seattle.

The vaccine will be tested in 13 U.S. cities, including Seattle, and in five other countries.

"This is an important step closer" to a vaccine that could be widely used, Corey said.

If the vaccine succeeds in the trial, a widely available immunization could be ready in about seven years, he said. A larger effectiveness trial would first be needed, as would reconstruction of the vaccine to cover additional variations of HIV.

"Right now, I think it's the best we've seen," said Dr. Julie McElrath, lead scientist in the Seattle arm of the trial and a Fred Hutchinson researcher.

Scientists have struggled since the mid-1980s to produce a vaccine, trying more than 100 preparations in animals and humans combined. But the virus is able to mutate, allowing it to escape an immune system primed by a vaccine to attack.

The trial, called the Step Study, will also be conducted in 13 U.S. cities and Puerto Rico, and in six cities abroad: Santo Domingo, Dominican Republic; Port-au-Prince, Haiti; Iquitos, Peru; Lima, Peru; Toronto, Canada; and Sydney, Australia.

In smaller trials involving more than 250 people, the vaccine has proved safe and shown encouraging immune response, Corey said. The worst side effects — in doses higher than the current trial — were fever and aches.

The vaccine, which is injected, uses a disabled form of a common cold virus, called adenovirus, to take three HIV genes into the body. The combination tricks the immune system into producing cells that would kill the whole AIDS virus. It is impossible for the vaccine itself to cause HIV infection.

In people previously infected with the type of adenovirus used in the vaccine — one of about 50 human adenoviruses — immune responses have not been as great as in others.

The use of adenoviruses in gene therapy against diseases has had a difficult history.

They were not successful in treating cystic fibrosis. And a relatively healthy 18-year-old man died five years ago during an experimental gene-therapy treatment for a rare liver disorder at the University of Pennsylvania. No one is sure what caused the fatal reaction.

Gene therapy, which uses viruses to ferry genes into the body to correct a problem, is different from a vaccine, however. And Corey said the new HIV vaccine uses an altered adenovirus that cannot reproduce and has more of its own genes removed to disable it than the one in the Pennsylvania experiment. The virus is injected into muscle, rather than directly into the liver as was the case in Pennsylvania.

In the new trial, volunteers will receive three injections over six months. Half will receive the vaccine, half will receive a placebo (a dummy vaccine) and no one, including the researchers, will know who gets what until the end of the trial. For about four years, each participant will be tested every six months for HIV.

All of the participants will be counseled against risky sex. But researchers expect some will still become infected. If they are, they will be monitored to see if the vaccine lowers the level of HIV in their blood.

The quest for an AIDS vaccine has been one of the most difficult in the history of medical science. More than 40 different vaccines have made it to initial trials in humans, but none has passed muster.

Five years ago, researchers announced that the only HIV vaccine ever widely tested was not effective. A three-year trial involving 5,400 volunteers in North America and Europe showed no difference in infection rates between those who received the vaccine and those who received a placebo.

Produced by VaxGen, the vaccine used a protein from the viral envelope to produce an antibody response to HIV. The body uses antibodies, "killer" cells and other cells to defend against diseases. In recent years, researchers have focused more on stimulating killer cells to attack HIV.

Soon after it was discovered in 1983 that AIDS is caused by a virus, scientists predicted a vaccine would be developed in five to 10 years. Now, they note how long it took for other vaccines: polio, 47 years; measles, 30; hepatitis A, 22; whooping cough, 20; and hepatitis B, 16.

Corey, an internationally known virologist and vaccine expert, has been in the search for an HIV vaccine since the beginning. He is more cautious now about predicting success anytime soon. But he is more enthusiastic than he has been in years about the cellular-immune response produced by the Merck vaccine.

"There is a lot of data to suggest that this level of response should do something," he said.

Warren King: 206-464-2247 or wking@seattletimes.com