HIV therapeutic vaccine research

[Guest guest]

HIV hopes ride on therapeutic vaccine

By DAVID WAHLBERG

The Atlanta Journal-Constitution

AIDS researchers, unable so far to concoct a vaccine powerful enough

to prevent infection in healthy people exposed to the virus, are

increasingly focusing on another approach: a vaccine to treat,

instead of prevent, HIV.

The idea of a therapeutic vaccine that would keep an infection in

check, not prevent it, presents new challenges and opportunities

that scientists will discuss at an Emory University conference

beginning today.

Safely mounting a strong immune response in people with HIV may be a

taller hurdle than protecting those without the virus.

But people with HIV might accept a higher risk of vaccine side

effects than those without the virus, experts say. And a therapeutic

vaccine, which might require only a few doses, may need to be only

partially effective to allow patients to stop taking costly

antiviral drugs, which most people in developing countries can't

afford.

" It could have a big impact on the epidemic, " said Rama Rao Amara,

an Emory researcher working on a therapeutic vaccine. " It's possible

you could take three shots and that would be it. "

Vaccines in global tests

Nearly 25 years after HIV was first reported, drugs and prevention

programs have had only minimal success in stopping the spread of the

virus.

" Only a vaccine can end the epidemic, " said Dr. Seth Berkley,

president of the International AIDS Vaccine Initiative in New York

City.

Most research has focused on a preventive vaccine. More than 30 such

vaccine candidates are in clinical studies globally, roughly two

dozen of them in the United States. One by Amara and his Emory

colleague Harriet is scheduled to enter its second small

study in people late this year.

The only preventive vaccine widely studied in people, made by VaxGen

of California, failed in trials two years ago. That vaccine has been

combined with another, by Sanofi Pasteur, for a major study in

Thailand; results are expected in a few years.

Another pharmaceutical company, Merck, launched a large study of a

new type of vaccine this year in several locations, including

Emory's Hope Clinic in Decatur. Like other newer vaccines, it uses a

virus to deliver scraps of HIV to the body's immune system so it

will recognize and attack the full-scale virus. Merck uses an

inactivated adenovirus, a cause of the common cold.

" That would be the lead candidate out there now, " Berkley said.

Cautious optimism

But therapeutic vaccines are also starting to show promise.

French researchers reported last November on a study of 18

Brazilians with HIV who had not started taking antiviral drugs. They

received a therapeutic vaccine that was individually tailored — by

removing certain immune cells from each patient, mixing those cells

with HIV in the lab, then reinjecting them. Four months later, the

level of virus in the patients' bloodstream had dropped an average

80 percent.

The French researchers will speak at Emory's conference on HIV

vaccine and drug development, held today and Friday. About 150

scientists will gather, including others from Europe and some from

Thailand.

A different therapeutic vaccine, by another French group, also

greatly reduced virus levels in a small study released this year.

Another recently studied in U.S. patients, including six patients at

Grady Memorial Hospital's Ponce de Leon Center in Atlanta, also

showed some benefit, said Dr. Lennox, medical director of

the clinic.

Scientists are intrigued but remain cautious, awaiting long-term

data. " We still don't know what's going to happen two or three years

down the line, " said , of Emory.

A major challenge remains for both therapeutic and preventive

vaccines: trying to activate both components of the human immune

system to fight HIV.

Most experimental HIV vaccines aim to make use of killer cells,

which hunt down cells infected by the virus and try to destroy them.

But researchers increasingly believe they also need to rally

antibodies, which prevent infection.

Vaccines for diseases such a polio and influenza use killed or

weakened viruses to generate antibodies. HIV is thought to be too

dangerous to use that way, plus it mutates quickly, easily dodging

antibodies.

But scientists have identified five rare HIV patients who have

naturally developed powerful antibodies against many strains of HIV,

Berkley said. Researchers are trying to figure out how the

protection was generated so they can harness the knowledge in a

vaccine.

" We've got the lock, " he said. " Now we have to find the key. "

At the Hope Clinic, Dr. Frances Priddy, medical director, said the

key to HIV vaccine research was enrolling volunteers in trials.

She is looking for 120 people — men and women at high risk for HIV —

to test the Merck vaccine candidate thought to be at the head of the

pack. About 3,000 people will be enrolled in the study globally.

The vaccine is designed to prevent HIV, but it may eventually also

be studied as a therapeutic vaccine.

No HIV vaccine is expected to be approved for years, or perhaps

decades. But since therapeutic vaccines could be allowed to carry

slightly more risk — and would only have to moderate disease, not

prevent infection — they may arrive more quickly.

" Therapeutic vaccines probably will be available before the

preventive ones, " Priddy said. " They don't have to be perfect. "

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