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October 9, 2000
PUBLIC HEALTH
A Shot in the Dark
HIV vaccines slow to come to light
By Debbie Carvalko

illustration: Skipper Chong Warson

It is a search nurse Eric Zimmerman launches each day in a clinic, a quest for which he's recruited his three teenage children, a battle that is literally in his blood: "There will be an HIV vaccine before I die," says Zimmerman, 51.

The 6-foot-tall, clear-spoken man is up to the task. He is the clinic coordinator at the Center for Immunization Research, in Baltimore, Maryland; in his spare time, he networks for the cause of HIV awareness and vaccine development. He speaks in community or education centers and at city, county, and state events -- and everywhere he goes he hands out pamphlets touting the need for vaccine volunteers. Zimmerman knows what he's asking: Every six weeks or so in 1998 and 1999, he entered a clinic as a patient himself during an HIV vaccine study. Blood was drawn from his arm to see if a test vaccine he was injected with triggered immunities that could keep people from contracting the virus.

Zimmerman says he is optimistic that an effective vaccine will be developed, and on the surface at least, there seems to be enough activity to justify his optimism.

sidebar: questions parents need to ask when medication is prescribed

At least 20 clinical trials of various HIV vaccines are underway nationwide. Initial tests using a DNA-based vaccine created by Merck & Co., based in New Jersey, began in January. Mid-level, or phase II, trials of a canary pox vaccine created at the University of Maryland are underway at Zimmerman's clinic. ALVAC, a vector vaccine created by Pennsylvania-based Aventis Pasteur, is in phase II trials. And VaxGen, a California-based developer, has AIDSVAX, which is in phase III testing, the final step before it is reviewed by the U.S. Food and Drug Administration (FDA).

But Zimmerman is also frustrated. "It takes so much time and money to move these things through the business and financial processes, just to do a study. The biggest problem now is that we don't have a lot of vaccines," he says.

Rose McCullough, executive director of the AIDS Vaccine Advocacy Coalition, in Washington, D.C., shares his ambivalence. "There is reason for optimism," says MuCullough, a microbiologist, "but there are many things that worry us" -- including not having enough vaccines in the final trials stages.

Too little, taking too long

Advocates are "thrilled" to see AIDSVAX in advanced trials, says McCullough. The maker says AIDSVAX triggers antibodies designed to bar HIV from reaching immune cells to destroy them. But the first test results of the vaccine's efficacy are not expected until October 2001. And plenty of scientists are skeptical about whether AIDSVAX will meet the minimum FDA requirement of 30 percent effectiveness, says McCullough.

"It is a good thing this phase III trial is happening," she offers. "We can learn from this, whether it is a yes or a no." But the trial makes one nagging reality more pronounced. "It is frustrating and disappointing that there are not more products out there. It is only by having a lot of products that we can have more than one ready to move into phase III trials. Here we are almost 20 years into the epidemic," exclaims McCullough, "and this is the very first phase III trial!"

Little money, low efforts

Since 1987, the National Institute of Allergy and Infectious Diseases (NIAID) has enrolled 3,357 volunteers in trials of 28 vaccines -- not very impressive numbers.

"Given the enormous nature of the problem, the global level of activity is outrageous," says Dr. Seth Berkley, president of the International AIDS Vaccine Initiative, based in New York City. "In the 16 years since the virus was discovered, no vaccine has been fully tested to see if it works, and the first one [that was developed] is only now in efficacy testing. More shocking is the limited pipeline of vaccines coming behind this one."

Wishing for a leader

Back in Maryland, Eric Zimmerman recalls the day he was recruited from his job as an agency nurse working at 17 different hospitals in Baltimore. The agency sent him to the vaccine research center in 1992. At the time, says Zimmerman, he had "no idea what was going on" with HIV vaccine research.

Within weeks, he signed on permanently. And he met Dr. Mary Lou Clements-Mann, the lead investigator on the center's study of a canary pox vaccine, and worked with her on the study before her death last year in a plane crash.

"She was a difficult woman to work for," remembers Zimmerman. Demanding. Driven. Insistent. A hands-on manager. "She devoted more than three years, day and night, to get the vaccine through the FDA."

Likewise, he and others involved in HIV vaccine research are committed to the cause. "This is a plague unlike any other we've ever seen," he comments. "Yet new vaccines keep getting stuck in pre-clinical testing." One vaccine being tested at Zimmerman's clinic was slated to be in phase III trials this year, but it keeps getting delayed. "We'll be lucky if it gets to phase III by 2002," he says.

Federal government ambivalent

Jorge Flores, chief of NIAID's vaccine clinical research branch, has great hopes for a vaccine. Bound for an international AIDS conference last July, Flores said preliminary tests of ALVAC show it may trigger cellular activity that can abort HIV soon after infection. "It is the best hope we have, clinically," explains Flores.

The government is also sponsoring trials of a combination vaccine using ALVAC and AIDSVAX. DNA vaccines are being tested as well.

He has great hopes, but he also has doubts. Flores reflects the same frustration as the others working toward the HIV vaccine goal: "There is a lot going on," he begins, "but there is not a lot [out there] that is very promising."

The solution? Dr. Berkley says it best: money and the right priorities.

"The world now spends about $20 billion a year on all aspects of AIDS treatments," Dr. Berkley explains, "but only about $50 million a year on product development ... This is less than 2 percent of the global resources and less than 10 percent of overall AIDS research."

The upside of personal commitment

At home, Zimmerman turns the talk to his children: Nate, 19; Gus, 16; and Kate, 13. "I take them with me to work. They know what is going on," he says, adding that his children have helped him hand out flyers at health fairs, festivals, and other events.

"Kate just helped me distribute flyers at the Gay Pride Festival," Zimmerman says, turning to his daughter, who is about to become a high school freshman.

"It's an important thing to do. It's a good thing my dad is doing," says Kate.

But Zimmerman shrugs off personal accolades. The good, he says, is being done by all people now involved in developing and testing vaccines or volunteering to be inoculated. "The upside of all this activity," Zimmerman explains, "is that a whole lot of work on basic immunology and virology is being done ... and someday that will translate to a vaccine that works."