Discovery of two antibodies raises hopes for scientists to come up with AIDS vaccine
04 09 09 - 17:23
Potent HIV-Blocking Proteins Raise Hopes for Vaccine
By Rob Waters - Bloomberg
Sept. 3 (Bloomberg) -- A new blood screening technique has turned up antibodies with the ability to neutralize many strains of the AIDS virus, a discovery that might help create a long- sought vaccine against the deadly disease.
The finding, published today in the journal Science, is the result of an global effort by AIDS researchers using new methods developed by two companies, Monogram Biosciences, a unit of Laboratory Corp. of America Holdings, and closely held Theraclone Sciences of Seattle. Scientists searched the blood of HIV-infected people who were symptom-free for three years.
The quest to develop an AIDS vaccine has consumed the energy of scientists and the cash of drug companies and funding agencies for 25 years, since the discovery of HIV, or human immunodeficiency virus. So far those efforts have failed. In 2007 Merck & Co. ended work on a vaccine after it appeared to boost people’s chances of becoming infected by HIV. Now the global alliance formed to hunt for antibodies able to block many strains of the AIDS virus has achieved its first success.
“We said if we want broadly neutralizing antibodies, we should look for people, infected individuals, who are making them,” said Dennis Burton, a scientist at the Scripps Research Institute, in La Jolla, California, who is at the center of the new undertaking. “The key thing about the antibodies we’ve found is that they’re more potent than previous ones and that’s great for a vaccine.”
Protocol G
The achievement was spearheaded by the International AIDS Vaccine Initiative, a New York-based nonprofit group that is coordinating and funding vaccine-development efforts. In 2006 the group kicked off an effort dubbed Protocol G, aimed at searching for antibodies that can neutralize the strains of HIV that circulate in the developing world, where the majority of new infections are taking place.
Working with doctors and clinics in Thailand, Australia, the U.S., the U.K. and especially Africa, where two-thirds of the world’s infected people live, the group collected blood samples from 1,800 people who had been infected with HIV for at least three years without developing symptoms.
Such people are the most likely to make antibodies, infection-fighting proteins, in their bloodstreams that can bar HIV from entering their blood cells and work against many or most of the HIV strains circulating in the world. At the end of a complex screening process, the effort pointed to two antibodies that came from one person in Africa.
A Variable Virus
“HIV is very variable, that’s the big problem with it,” Burton said in a telephone interview yesterday. “If you want to make a vaccine that works, it has to protect against not just one but most of the strains that are out there.”
After collecting blood from the 1,800 people, the samples were shipped to the South San Francisco research labs of Monogram Biosciences. Monogram had developed a technique for embedding in a virus an enzyme that would glow if it entered a cell. Using robotic technology, they mixed the virus carrying the enzyme with the blood cells from the 1,800 people and watched what happened.
“When you see the light you know your virus has successfully entered and infected the target cell,” said Christos Petropoulos, Monogram’s chief scientific officer, in a telephone interview yesterday. No light meant that the patient’s antibodies had kept the virus from getting in the cell.
Laboratory Corp. rose 22 cents, or less than a percent, to $69.09 at 4:04 p.m. in New York Stock Exchange composite trading. The shares of the Burlington, North Carolina-based company have declined 7 percent in 12 months. The stock traded today as low as $68.28 before Bloomberg News reported the results, and rose afterward.
Theraclone Sciences
Monogram’s process allowed the scientists to find the blood samples that most successfully avoided infection. Next they needed to isolate the antibodies themselves, and for this they turned to Theraclone Sciences, which had developed another critical technology.
The Theraclone team isolated some 30,000 antibody-making cells from blood samples of an African donor that ranked high in ability to prevent infection and cloned them to make multiple copies of each antibody. The individual antibodies were then tested again using Monogram’s system to find those that blocked the greatest number of HIV strains.
The two antibodies from the African donor each blocked about three-quarters of the 162 HIV strains they were tested against, scientists said.
The antibodies themselves can’t simply be put in a vaccine to immunize people against HIV, said Wayne Koff, senior vice president of research and development at the Vaccine Initiative in New York. While such an effort could have a short-term benefit, a successful vaccine will teach people’s immune systems to produce their own powerful antibodies.
Spikes on Virus
The researchers also were able to look at the sites where the antibodies bound to proteins on a spike on the surface of the HIV virus. Koff and his colleagues think this spike may represent a vulnerable part of the virus and tracing how these and other potent antibodies attach to it may help them to better map its structure and design a vaccine, he said.
“We’re like sculptors trying to make a key that fits a lock and we’re starting with a lump of clay,” Koff said in a telephone interview yesterday. “These antibodies have given us information on the general shape of the key and as we learn more about the binding site, we’ll have a pretty close approximation of what the key actually looks like.”
The Protocol G effort will continue to hunt for additional HIV neutralizing antibodies and to decipher the structure of a virus that has so far outwitted many attempts to defeat it. While a vaccine is still years away, Burton said scientists are making progress by learning from the very people who appear to be dodging the AIDS bullet.
To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.