AIDS Vaccine Testing at Crossroads

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AIDS Vaccine Testing at Crossroads

After Little Progress in 25 Years, Scientists Urge Return to Basic

Research By Brown, Washington Post Staff Writer

Wednesday, March 26, 2008; A04

The leaders of the federal government's effort to develop an AIDS

vaccine said yesterday that more of their budget needs to be spent on

basic lab research and less on testing the current crop of vaccines,

none of which has proved useful in human trials.

The declaration made at a " summit meeting " is tantamount to an

admission that almost no progress has been made in the search for an

AIDS vaccine in the past 25 years and that something close to new

start is necessary.

The conference, held at the National Institutes of Health in Bethesda,

was called after a much-touted vaccine tested in half a dozen

countries not only failed to benefit people who received it but also

may have actually increased their chance of becoming infected with

HIV, the virus that causes AIDS.

" We need to turn the knob toward [basic scientific] discovery --

nobody should be unclear about that, " said S. Fauci, head of

the National Institute of Allergy and Infectious Diseases.

One of the co-chairmen of the meeting, Warner C. Greene of the

University of California at San Francisco, was more definitive in his

assessment. " There is no question the AIDS vaccine enterprise is in

need of a major mid-course correction, " he told the gathering of about

300 scientists, who came from as far away as South Africa and Kenya

for the one-day meeting.

Carl W. Dieffenbach, the head of the NIH's Division of AIDS,

acknowledged that " this summit does mark a change in our approach. "

The meeting was called after two studies testing the same vaccine were

stopped in September. The vaccine, made by the pharmaceutical giant

Merck, used a crippled version of a common respiratory virus, called

adenovirus type 5, to deliver a selection of HIV proteins to the

immune system in the hope of inducing protection.

The studies were stopped when early results suggested that people

receiving the vaccine were more likely to become infected with HIV

than people receiving placebo injections. The reason is unknown and

the subject of intensive scientific study.

NIH is spending $497 million on AIDS vaccine research this year, with

about $476 million going to researchers outside its campus. About 47

percent of the money funds basic research and 38 percent funds testing

" candidate vaccines " in humans. Fauci said the ratio needs to be

tipped more steeply in favor of basic research.

Although researchers have tested numerous AIDS vaccines on small

groups of volunteers, only three vaccines have gone to large clinical

trials with thousands of volunteers.

Earlier this decade, one product, called AIDSVAX, was found to be

ineffective. The Merck vaccine, which showed promising results in

monkeys, may have been harmful. A third vaccine, being tested in an

experiment nearing completion in Thailand, is given little hope of

working by most researchers, 21 of whom wrote a letter to the journal

Science several years ago saying that the study should not even begin.

The search for an AIDS vaccine has proved difficult for several reasons.

Successful vaccines mimic the protection the body normally provides

when confronted with a virus, bacterium or other microbe. HIV,

however, mainly attacks immune system cells, which are the ones a

vaccine is trying to enlist for help.

Furthermore, unlike most viruses, HIV stitches itself permanently into

the DNA of some human cells after entering them. That means that if a

vaccine does not provide full protection within days -- and possibly

even hours -- of exposure, irreversible infection occurs.

A few people who become infected with HIV are able to survive without

treatment indefinitely -- so-called elite controllers. Many non-human

primates also tolerate the monkey equivalent of HIV without becoming

ill. In both cases, how the immune system achieves that outcome is

unknown.

" We do not have a vaccine now. . . . We are not only not there, we are

not close, " said Hoxie, a researcher at the University of

Pennsylvania, who summarized the view of a panel of basic researchers

who spoke at the meeting.

One organization yesterday called for the money now spent on AIDS

vaccine research to be used for HIV testing, treatment of HIV patients

and research on the use of antiretroviral drugs to prevent infection.

" I think we should pull the plug on vaccine research, " said

Weinstein, president of the AIDS Healthcare Foundation, a private,

nonprofit group that provides treatment for people with HIV.

" Do we have any other enterprise that has been studied for 25 years

and for which we've spent billions of dollars where we have no

results? There's no evidence we'll ever have an AIDS vaccine, " he said.

However, Warren of the AIDS Vaccine Advocacy Coalition, who

attended the meeting, praised it as the beginning of a necessary

readjustment of priorities.

" We are at a critical moment in the field. We've had a tremendous

setback. But this field is not abandoning the research for a vaccine, "

he said. " This is not the end of the line for AIDS vaccine research.

That was an important point for everyone. "

Several people at the meeting said that they not only support greater

spending on basic research, but also that the government must be

willing to fund promising, yet unorthodox, proposals, or a generation

of young scientists may abandon AIDS research in favor of fields that

are less challenging.

http://www.washingtonpost.com/wp-dyn/content/article/2008/03/25/AR2008032503153.\

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