TUESDAY, DECEMBER 3, 2002
BATTLING THE BEAST
THE UNIVERSITY DAILY KANSAN = 5A
HIV vaccine question one of several projects
Shilpa Buch double checks her assistant's observance of a stage of the virus. A staff of 16 researchers are working on a vaccine for the HIV virus to be presented to the FDA this spring.
A lab assistant measures out bacteria to be grown inside an auger petri dish. Scientists at the KU Medical Center studied various forms of the HIV virus in the lab.
Freezers inside the lab house dormant samples of SHIV-KU, a combined version of the human and simian immunodeficiency viruses. SHIV-KU was developed specifically for the Med Center's vaccine prototype. The virus grows into full-blown AIDS in two weeks.
Although creating a deadlier virus might scare some, Narayan said the hybrid would not be as harmful in humans. Even so, the team is taking extreme precautions to prevent outbreak, he said.
Toward the back of the grid of black counter tops in the lab at the Med Center in Kansas City, Mo., sits the door to the "beast" itself. Almost hidden, the door has a sign warning of the biohazard that awaits inside.
The lab, designated at the highest level of caution, is designed to prevent fluke infections. Every machine is shielded by a clear plastic cover to ensure that nothing pathogenic spills out in case the machinery breaks down.
Several of the work stations are enclosed. Under one hood, a researcher maneuvers his arms through a small space under a plastic shield, illuminated by a fluorescent light at the top of the enclosed box. The workstation uses a weak vacuum to suck away stray particles of the virus.
Even with so many precautions, Buch said common sense was the most important tool for a researcher to avoid infection.
"People have used hands to push down the toxic waste in the trash can before," she said, pointing to an orange waste basket filled with used syringes. "They have been poked."
But none of the researchers has been infected, she said. Therace to approval
Instead of following precedent and testing the monkeys with pure SIV, Narayan and his team developed the deadlier hybrid to maximize the number oftimes the vaccine can be tested for effectiveness in each monkey. In the procedure, team members vaccinate six monkeys and allow their immune systems to build a defense for six months before testing the vaccine's strength against SHIV-KU.
They challenge the vaccine with SHIV-KU again at the one-year, one-and-a-half-year, two-year and three-year marks.
The repeated testing gives the Med Center group a competitive edge, Narayan said. The country's two other DNA vaccine labs
give monkeys vaccines and settle with results after challenging them with SIV two weeks later.
To emphasize the importance of repeated testing, Narayan said that a previous vaccine his team had developed began to weaken after three years, meaning researchers would have to reinject the vaccine to prevent the death of the monkeys.
Although SHIV-KU and HIV are similar and share many of the same genes, they're not the same. For that reason, any successes in the primate testing stages must be verified with a true HIV vaccine through human clinical trials.
This is the team's second attempt at advancing a vaccine to human clinical trials. Last year, Narayan approached the Food and Drug Administration with a live vaccine prototype that he said had performed well in the lab and prevented infection in monkeys. But the organization didn't approve the prototype because it appeared to pose too many risks. All HIV vaccines now being tested in humans have come from man-made materials that cannot cause HIV infection.
"Even though the FDA would not accept it for its use, we still know it works," Narayan said.
The rejection caused the team to focus on its current DNA prototype. Since the vaccine uses only the virus's DNA, it hasn't performed as well as its live counterpart, Narayan said. Even though he isn't as happy with this form, he said he expected FDA approval.
According to an FDA Website, the organization's policy prohibits commenting about clinical trials for diseases that are in the review process.
Prevention, not a cure
A potential HIV inoculation from the Med Center team wouldn't provide a cure for the disease. It would protect only the uninfected. Narayan said nothing so far could hold back the virus entirely.
"In a week, HIV has blown you away," he said.
A drug cocktail designed to curb HIV replication can only knock the "virus burden," or virus
count, to a low level, he said
"People become relaxed because they think they've got a cure," he said. "But as soon as they stop taking the drugs it comes rolling back."
For that reason, he has focused on prevention rather than a cure.
Narayan began looking at a family of lenti viruses — a group of slow-acting viruses to which HIV belongs — during his post-doctoral work at Johns Hopkins University, Baltimore, Md.
Narayan's studies began before AIDS broke into the limelight. While expressing concern for those suffering from the disease, he said he pursued an HIV vaccine to satiate a hunger for a challenge.
"If it has human spin-off — great," he said. "I'm not an angel. I do it for myself."
Narayan doesn't perform much hands-on work. Instead, he coordinates the team's w-rk.
Although Narayan expects a promotion to human clinical trials for the DNA vaccine, he said the team worked against strong odds that the project would flop.
"The virus outwits me about every time," he said.
For that reason, the team is trying several approaches at once to increase the chances of finding a successful one.
"We've got a lot of irons in the fire. It's like a pipeline with the input here and the output here," he said, gesturing along an imaginary pipeline running before him. "You can't wait. You have to keep feeding the pipeline."
If one of the team's experiments fails, the team cannot afford to have nothing else in progress as backup, he said.
Pinning down a permanent variation of HIV has been nearly impossible, Buch said. The virus mutates slightly and frequently, so creating a vaccine will not protect against all strains of the virus. The key is finding the most prevalent strain and pursuing it fully, she said.
"You cannot say you've had full victory," she said, "but partial victory.
Edited by Adam Pracht
Human testing coming stage for HIV vaccine
By Lindsay Hanson
By Lindsay Hanson
lhanson@kansan.com
Kansan staff writer
Although Bill Narayan and his HIV vaccine lab team are prepped to break into the elite level of human testing, getting FDA approval is years in the future.
Before the Food and Drug Administration will approve an HIV vaccine for distribution, candidates must prove themselves in three phases of clinical tests.
Phase I, which could last two years, finds volunteers to test for safety and to look for side effects.
Researchers can't legally give people HIV to test the vaccine, said Narayan, chairman of microbiology, molecular genetics and immunology at the University of Kansas Medical Center. The team would recruit no more than 20 volunteers at risk for HIV, he said.
Among those in what he called high-risk communities — promiscuous people, homosexuals and intravenous drug users—Narayan said he would recruit homosexuals the most heavily because he thought he could depend on them to follow through with the tests.
If volunteers' bodies tolerate the vaccine, it will move to Phase II trials. Researchers add to the volunteer pool and concentrate heavily on the body's immune response over a period of two years.
The most promising prototypes break into Phase III trials, although none has reached this phase yet. In these efficacy, or effectiveness, trials, researchers cast thousands of volunteers at the highest risk of HIV exposure.
Because Phase III trials require a wide network of statisticians and infectious disease representatives. Narayan said the team would not have the funds to conduct them without support from an outside company. This most crucial and trying phase can last four years.
According to NIAID's Website, efficacy trials will succeed if they recruit volunteers who are already at high risk for the disease and who follow through with the study.
— Edited by Adam Prach+
Shilpa Buch, assistant research professor in microbiology, molecular genetics, and immunology at KU Med, is part of a team of researchers looking for HIV vaccines.
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