Antibody find lifts HIV vaccine hopes

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Antibody find lifts HIV vaccine hopes

Leigh Dayton, Science writer | September 04, 2009 The Australian

HIV researchers have made the biggest breakthrough in 15 years, identifying two

powerful antibodies that appear to fight all types of the virus - a development

that brings new hope of a vaccine.

Using powerful screening technology, a US team has discovered two

infection-fighting proteins in blood taken from an African who was already

infected with HIV but did not show any of the symptoms.

The scientists found these antibodies apparently neutralised all major groups,

or clades, of HIV.

By determining where the antibodies bind to the virus, they know which parts of

the virus to target with vaccines. They also identified what genes the donor's

body used to build the " broadly neutralising antibodies " .

The knowledge could lead to gene therapies to treat people already infected with

HIV, as well as vaccines to protect people from infection.

Worldwide, 33 million people are infected with HIV, including about 16,600

Australians. The virus is estimated to kill about 2 million people a year,

having already claimed 25 million.

Antibodies are found in the blood and other body fluids and are produced when a

person's immune system detects harmful substances such as live viruses or

bacteria.

The newly found antibodies, PG9 and PG16, target regions of the virus that

remain constant, even as the virus mutates.

The findings were reported overnight in the journal Science by an international

consortium led by immunologist Dennis Burton of the Scripps Research Institute

in La Jolla, California, and the newly established Ragon Institute in Boston,

Massachusetts.

" We're very, very excited to see this paper, " said virologist Damian Purcell,

head of Melbourne University's Molecular Virology Laboratory.

" It's a really important finding for vaccine developers. "

New-York based Wayne Koff, senior vice-president of research and development

with the International AIDS Vaccine Initiative, said the findings represented

" an exciting advance toward the goal of an effective AIDS vaccine because now

we've got a new, potentially better target on HIV to focus our efforts for

vaccine design " .

" And having identified this one, we're set up to find more, which should

accelerate global efforts in AIDS vaccine development, " he added.

Trial vaccines developed over the past 15 years have proved ineffective or even

dangerous.

In November 2007, a global vaccine trial involving 3000 people at high risk of

HIV infection, including 19 Australians, was halted when scientists discovered

that the vaccine appeared to make them more susceptible to HIV infection. The

reason remains unclear.

Associate Professor Purcell cautioned that the research was in its early days

but he predicted that, with the new results in hand, scientists would solve key

technical problems within five years and have vaccines and therapies on the

market in another 10 years, at the latest.

" This finding demonstrates that, after all the disappointments over the last 15

years, scientists have gone back to basics and we're looking at fundamental

questions like what are the best targets in the virus, " Professor Purcell said.

He hopes to use the newfound antibodies to test candidate vaccines that appear

to work in animals.

According to Professor Purcell, teams like his were frustrated that approaches

that had worked with other viruses were not working with HIV.

Part of the problem was that HIV mutated rapidly in the community and even in an

infected person's body. Further, numerous clades circulated in different regions

of the world.

As well, because no one is known to have completely eliminated an HIV infection,

it's not known which elements of the body's immune response must be triggered to

get rid of, or clear, the virus.

Until now, researchers had been unable to find an Achilles heel on the virus

that remained the same across clades.

Professor Burton's group discovered that the special antibodies, PG9 and PG16,

targeted regions of the virus that didn't change, despite viral mutations.

Teams worldwide can now use the finding to devise immunogens -- the active

ingredients of vaccines -- that stimulate a person's immune system to create

similar highly protective antibodies.

Professor Burton's group began by collecting blood samples from 1800

HIV-infected people who had remained symptom-free for years. These " elite

controllers " are able to suppress the virus without the use of drugs.

According to Professor Purcell, elite controllers achieve that in a variety of

ways: from blocking the ability of the virus to infect other cells to eliciting

other types of immune responses. Rough estimates are that one in 300 infected

people are elite controllers.

Blood samples used in the study came from seven African nations, as well as

Thailand, Britain, the US and Australia.

The Australian samples were supplied by Melbourne's National Reference

Laboratory.

Applying a series of sensitive screening procedures and specially designed

technology, Professor Burton's team identified which antibodies were most

effective. From the top 10per cent, they identified the PG9 and PG16 antibodies,

then isolated the gene coding for them, enabling production of colonies of the

antibodies.

These will be available to laboratories worldwide.

Professor Burton said: " So now we may have a better chance of designing a

vaccine that will elicit such broadly neutralising antibodies, which we think

are key to successful vaccine development. "

http://www.theaustralian.news.com.au/story/0,25197,26024602-601,00.html