Tuesday, July 04, 2006

HIV - $2.2 million machine speeds antibody search process

$2.2 million machine speeds antibody search process
By Bruce Lieberman
C opyright by UNION-TRIBUNE
June 6, 2006


The Scripps Research Institute
Scientists hope CrystalMation will help them in the search for new HIV antibodies.
In a building at The Scripps Research Institute in La Jolla, scientists are taking giant steps toward creating the world's first HIV vaccine.

Yesterday, the researchers unveiled a $2.2 million machine called CrystalMation. The device, which can rapidly screen protein molecules, will vastly accelerate the search for powerful antibodies against HIV, the virus that causes AIDS.

The announcement came on the 25th anniversary of the first medical description of the condition later known as acquired immune deficiency syndrome.

CrystalMation is the centerpiece of an international effort to develop a vaccine against AIDS. Complications related to AIDS have killed 25 million people worldwide – 500,000 of them in the United States – since it was officially identified.

AIDS likely will kill 100 million people by the time a vaccine is available, said Dr. Seth Berkley, president and CEO of the International AIDS Vaccine Initiative in New York City. Berkley's group helped to pay for CrystalMation.

“Clearly, without better tools and a better strategy, we're not going to get there,” said Berkley, who attended yesterday's unveiling. “Our mission is to ensure the development of a safe, effective and accessible HIV vaccine for use throughout the world.”

In 2002, the Scripps institute and Berkley's group launched the Neutralizing Antibody Consortium to attack the AIDS problem. Members include scientists from Scripps, Harvard University, Cornell University, the University of Pennsylvania and those from England and Switzerland.

The consortium's researchers collaborate on AIDS projects and will share data produced from CrystalMation, which is built by the Carlsbad firm Rigaku Automation Inc.

CrystalMation allows scientists to quickly crystallize proteins, an otherwise laborious but critical step in the search for new antibodies against HIV.

A robotic arm in CrystalMation mixes protein molecules with various chemicals that help crystallize the proteins. This process essentially fixes them in place so researchers can examine their structures with a technique called X-ray crystallography.
The ability to visualize these antibody candidates is vital if scientists hope to develop a vaccine that induces a person's immune system to produce real antibodies.

It can take one to two years to manually prepare a crystallized protein suitable for analysis by X-ray crystallography.

With CrystalMation, scientists hope to produce 100 to 200 protein structures annually. It's a hugely ambitious goal that requires many trial runs for each protein molecule.

“This is why the robot is so important,” said Ian Wilson, a Scripps institute researcher and consortium scientist. “To do this by hand . . . would be impossible. It would take years and years and years and years.”

In traditional vaccine development, a disabled version of a virus prompts an immune response that produces natural antibodies against the real thing. That approach doesn't work with AIDS, in large part because of HIV's tremendous ability to mutate rapidly.

“Variability is the 800-pound gorilla that sits on the shoulders of all the people who work on HIV,” said Dennis Burton, a Scripps institute scientist and director of the Neutralizing Antibody Consortium.

In the case of HIV, “what a vaccine has to do is induce antibodies that can neutralize essentially all of these different viruses,” Burton said.

Scientists have identified a few spots on HIV that could be vulnerable to antibodies – so-called “chinks in the armor.” These are places on the virus where antibody proteins could recognize it as a foreign entity, then attach themselves to it and disable it.

CrystalMation is expected to help researchers engineer antibodies that can exploit such weaknesses.

“The idea is to create, basically, super-antibodies that will neutralize (HIV),” Berkley said. “That would be the Holy Grail.”

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