http://www.iavi.org/research-development/IAVI-RD-Programs/Pages/NewAntibodiesFoundthatCrippleHIV.aspx

IAVI and affiliated researchers have discovered two powerful new antibodies to HIV that reveal what may be an Achilles heel on the virus. The findings are the result of a worldwide effort launched by IAVI in 2006 to find new antibodies that neutralize a wide variety of strains of HIV circulating in the world. The study was published in the journal Science.

HIV, the virus that causes AIDS, is the most mutable pathogen ever encountered by modern science. It changes at a furious rate, which helps it evade the body’s immune system. Today, countless variations of the virus infect people around the world. To be effective an AIDS vaccine would have to work against many versions of HIV.

The two new broadly neutralizing antibodies are the first to be discovered in more than a decade, and the first to be isolated from donors in developing countries where the pandemic is raging. Now researchers will try to exploit the newfound vulnerability on the virus to craft new approaches to designing an AIDS vaccine.

 “The findings are an exciting advance because now we’ve got a new, potentially better target on HIV to focus our efforts for vaccine design,” said Wayne Koff, senior vice president of research and development at IAVI. “And having identified this one, we’re set up to find more.”

What are broadly neutralizing antibodies?

Antibodies are infection-fighting protein molecules that tag, neutralize and help destroy toxins and invading pathogens. They are secreted by immune cells known as B lymphocytes (a kind of white blood cell) in response to stimulation by antigens, which are molecules found on the invading pathogen. Each antibody binds only to the specific antigen that stimulated its production. HIV attacks and quickly overwhelms the body’s immune system, but a minority of people naturally produce broadly neutralizing antibodies—ones that target multiple strains of HIV and prevent the virus from infecting cells. Isolating these antibodies gives vaccine researchers valuable insight into fighting the virus.

Why is this discovery important?

Before this discovery, researchers had found just four antibodies widely considered to be broadly neutralizing, and those four were associated with a strain of the virus circulating primarily in the Americas, Europe and Australia. The new antibodies came from a donor in the developing world, where 95% of new infections occur.

They also reveal a new vulnerable spot on HIV, binding to a potentially easier-to-reach patch on the virus that no previously known antibodies targeted. This is extremely important—it provides a new target for vaccine designers to exploit. And the antibodies appear to be highly potent as well, which means they bind to the virus tightly.  This is important because—if they can be elicited by vaccination—the body might not have to produce large amounts of the antibodies to gain protection from HIV.

What’s the next step?

The new antibodies will now be closely studied by researchers in IAVI’s Neutralizing Antibody Consortium, who will work out the molecular structure and the precise mechanism by which the antibodies bind to HIV. With this information in hand, they will begin working to design novel immunogens—the active ingredient in vaccines—to elicit these antibodies in all people. If they succeed, the immunogens will be put through the preclinical process to produce an industrially viable vaccine candidate for further development.

 How were the antibodies found?

The discovery of the new antibodies is the result of a global collaboration among IAVI, the Scripps Research Institute, private biotech firms and more than a dozen clinical research centers around the world.  Learn more

By Victoria Gill Science reporter, BBC News The synthetic cell looks identical to the ‘wild type’Scientists in the US have succeeded in developing the first synthetic living cell.

Dr Craig Venter says yeast, chemicals, and computers were used by scientists

The researchers hope eventually to design bacterial cells that will produce medicines and fuels and even absorb greenhouse gases.

The team was led by Dr Craig Venter of the J Craig Venter Institute (JCVI) in Maryland and California.

He and his colleagues had previously made a synthetic bacterial genome, and transplanted the genome of one bacterium into another.

Now, the scientists have put both methods together, to create what they call a “synthetic cell”, although only its genome is truly synthetic.

Dr Venter likened the advance to making new software for the cell.

The researchers copied an existing bacterial genome. They sequenced its genetic code and then used “synthesis machines” to chemically construct a copy.

Dr Venter told BBC News: “We’ve now been able to take our synthetic chromosome and transplant it into a recipient cell – a different organism.

“As soon as this new software goes into the cell, the cell reads [it] and converts into the species specified in that genetic code.”

The new bacteria replicated over a billion times, producing copies that contained and were controlled by the constructed, synthetic DNA.

“This is the first time any synthetic DNA has been in complete control of a cell,” said Dr Venter.

‘New industrial revolution’Dr Venter and his colleagues hope eventually to design and build new bacteria that will perform useful functions.

WATTS WHAT…

Continue reading the main story

Even some scientists worry we lack the means to weigh up the risks such novel organisms might represent, once set loose

Susan Watts BBC Newsnight science editor Read Susan Watts’s thoughts

“I think they’re going to potentially create a new industrial revolution,” he said.

“If we can really get cells to do the production that we want, they could help wean us off oil and reverse some of the damage to the environment by capturing carbon dioxide.”

Dr Venter and his colleagues are already collaborating with pharmaceutical and fuel companies to design and develop chromosomes for bacteria that would produce useful fuels and new vaccines.

But critics say that the potential benefits of synthetic organisms have been overstated.

Dr Helen Wallace from Genewatch UK, an organisation that monitors developments in genetic technologies, told BBC News that synthetic bacteria could be dangerous.

“If you release new organisms into the environment, you can do more harm than good,” she said.

“By releasing them into areas of pollution, [with the aim of cleaning it up], you’re actually releasing a new kind of pollution.

“We don’t know how these organisms will behave in the environment.”

Dr Wallace accused Dr Venter of playing down the potential drawbacks.

“He isn’t God,” she said, “he’s actually being very human; trying to get money invested in his technology and avoid regulation that would restrict its use.”

But Dr Venter said that he was “driving the discussions” about the regulations governing this relatively new scientific field and about the ethical implications of the work.

Continue reading the main story

The risks are unparalleled, we need safety evaluation for this kind of radical research and protections from military or terrorist misuse

Julian Savulescu Oxford University ethics professor

He said: “In 2003, when we made the first synthetic virus, it underwent an extensive ethical review that went all the way up to the level of the White House.

“And there have been extensive reviews including from the National Academy of Sciences, which has done a comprehensive report on this new field.

“We think these are important issues and we urge continued discussion that we want to take part in.”

Dr Gos Micklem, a geneticist from the University of Cambridge, said that the advance was “undoubtedly a landmark” study.

But, he said, “there is already a wealth of simple, cheap, powerful and mature techniques for genetically engineering a range of organisms. Therefore, for the time being, this approach is unlikely to supplant existing methods for genetic engineering”.

The ethical discussions surrounding the creation of synthetic or artificial life are set to continue.

Professor Julian Savulescu, from the Oxford Uehiro Centre for Practical Ethics at the University of Oxford, said the potential of this science was “in the far future, but real and significant”.

“But the risks are also unparalleled,” he continued. “We need new standards of safety evaluation for this kind of radical research and protections from military or terrorist misuse and abuse.

“These could be used in the future to make the most powerful bioweapons imaginable. The challenge is to eat the fruit without the worm.”

life’ breakthrough announced by scientists

Page last updated at 16:52 GMT, Thursday, 20 May 2010 17:52 UK

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