Advance in Quest for HIV Vaccine

[Guest guest]

Just saw this online and thought I'd share.

From the Wall Street Journal:

http://online.wsj.com/article/SB10001424052748703609004575355072271264394.html

JULY 9, 2010

Advance in Quest for HIV Vaccine

By MARK SCHOOFS

HIV research is undergoing a renaissance that could lead to new ways

to vaccinate against the AIDS virus and other viral diseases.

In the latest development, U.S. government scientists say they have

discovered three powerful antibodies, the strongest of which

neutralizes 91% of HIV strains, more than any AIDS antibody yet

discovered. They are now deploying the technique used to find those

antibodies to identify antibodies to influenza viruses.

Mark Schoofs discusses a significant step toward an AIDS vaccine, U.S.

government scientists have discovered three powerful antibodies, the

strongest of which neutralizes 91% of HIV strains, more than any AIDS

antibody yet discovered.

The HIV antibodies were discovered in the cells of a 60-year-old

African-American gay man, known in the scientific literature as Donor

45, whose body made the antibodies naturally. The trick for scientists

now is to develop a vaccine or other methods to make anyone's body

produce them as well.

That effort " will require work, " said Nabel, director of the

Vaccine Research Center at the National Institute of Allergy and

Infectious Diseases, who was a leader of the research. " We're going to

be at this for a while " before any benefit is seen in the clinic, he

said.

The research was published Thursday in two papers in the online

edition of the journal Science, 10 days before the opening of a large

International AIDS Conference in Vienna, where prevention science is

expected to take center stage. More than 33 million people were living

with HIV at the end of 2008, and about 2.7 million contracted the

virus that year, according to United Nations estimates.

Vaccines, which are believed to work by activating the body's ability

to produce antibodies, eliminated or curtailed smallpox, polio and

other feared viral diseases, so they have been the holy grail of AIDS

research.

Last year, following a trial in Thailand, results of the first HIV

vaccine to show any efficacy were announced. But that vaccine reduced

the chances of infection only by about 30%, and controversy erupted

because in one common analysis the results weren't statistically

significant. That vaccine wasn't designed to elicit the new

antibodies.

The new discovery is part of what Wayne Koff, head of research and

development at the nonprofit International AIDS Vaccine Initiative,

calls a " renaissance " in HIV vaccine research.

Antibodies that are utterly ineffective, or that disable just one or

two strains, are common. Until last year, only a handful of " broadly

neutralizing antibodies, " those that efficiently disable a large swath

of HIV strains, had been discovered. And none of them neutralized more

than about 40% of known HIV variants.

But in the past year, thanks to efficient new detection methods, at

least a half dozen broadly neutralizing antibodies, including the

three latest ones, have been identified in peer-reviewed journals.

Dennis Burton of the Scripps Institute in La Jolla, Calif., led a team

that discovered two broadly neutralizing antibodies last year; he says

his team has identified additional, unpublished ones. Most of the new

antibodies are more potent, able to knock out HIV at far lower

concentrations than their previously known counterparts.

HIV is a highly mutable virus, but one place where the virus doesn't

mutate much is where it attaches to a particular molecule on the

surface of cells it infects. Building on previous research,

researchers created a probe, shaped exactly like that key site, and

used it to attract only those antibodies that efficiently attack it.

That is how they fished out of Donor 45 the special antibodies: They

screened 25 million of his cells to find 12 that produced the

antibodies.

Journal Community

Donor 45's antibodies didn't protect him against HIV. That is likely

because the virus had already taken hold before his body produced the

antibodies.

While he has produced the most powerful HIV antibody yet discovered,

researchers say they don't know of anything special about his genes

that would make him unique. They expect that most people would be

capable of producing the antibodies, if scientists could find the

right way to stimulate their production.

Dr. Nabel said his team is applying the new technique to the influenza

virus. Like HIV, influenza is a highly mutable virus—the reason a new

vaccine is required every year.

" We want to go after a universal vaccine " by using the new technique

to find antibodies to a " component of the influenza virus that doesn't

change, " said NIAID director Fauci. In principle, Dr. Fauci

said, the technique could be used for any viral disease and possibly

even for cancer vaccines.

Some of the new HIV antibodies discovered over the past year attack

different points on the virus, raising hopes that they could work

synergistically.

In unpublished research, Mascola, deputy director of the Vaccine

Research Center, has shown that one of Dr. Burton's antibodies

neutralizes virtually all the strains that are resistant to the

antibody from Donor 45. He also found the reverse: The antibody from

Donor 45 disables HIV strains resistant to one of Dr. Burton's best

antibodies. Only one strain out of 95 tested was resistant to both

antibodies, he said. Dr. Mascola is one of the authors of Thursday's

papers.

Researchers say they plan to test the new antibodies, likely blended

together in a potent cocktail, in three broad ways.

First, the antibodies could be given to people in their raw form,

somewhat like a drug, to prevent transmission of the virus. But they

would likely be expensive and last in the body for a limited time,

perhaps weeks, making that method impractical for all but specialized

cases, such as to prevent mother-to-child transmission in childbirth.

The antibody could also be tested in a " microbicide, " a gel that women

or gay male partners could apply before sex to prevent infection.

The antibodies might even be tried as a treatment for people already

infected. While the antibodies are unlikely to completely suppress HIV

on their own, say scientists, they might boost the efficacy of current

antiretroviral drugs.

Dr. Nabel said that the Vaccine Research Center has contracted with a

company to produce an antibody suitable for use in humans so that

testing in people could begin.

A second way to use the new research is to deploy classical vaccine approaches.

In a study published this year in the Proceedings of the National

Academy of Sciences, scientists at Merck & Co. provided what Dr. Koff

calls a " proof of principle " that other researchers can build on. They

began with an old antibody, weaker than the newly discovered ones,

that attaches to a particular part of HIV. They then created a replica

of a vulnerable piece of the virus, to train the immune system to

produce antibodies aimed at that exact spot. It was a painstaking

process, requiring researchers to add chemical bonds to stabilize the

replica so that it wouldn't collapse. Eventually, Merck was able to

make experimental vaccine candidates capable of spurring guinea pigs

and rabbits to produce the antibody.

There are other potential pitfalls. There is evidence that Donor 45's

cells took months or possibly even years to create the powerful

antibodies. That means scientists might have to give repeated booster

shots or devise other ways to speed up this process.

Finally, there are experimental methods that employ tactics such as

gene therapy. Nobel laureate Baltimore is working on one such

approach.

His team at the California Institute of Technology in Pasadena,

Calif., has stitched genes that code for antibodies into a harmless

virus, which they then inject into mice. The virus infects mouse

cells, turning them into factories that produce the antibodies.

Write to Mark Schoofs at mark.schoofs@...

**

danielbfc@...

" Never doubt that a small group of thoughtful, committed people can change the

world. Indeed it is the only thing that ever has. "

~~ Margaret Mead