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Antibody not fooled by tricky HIV -U.S. report
Researchers said on Thursday they had figured out how a rare antibody sees past the disguises of the AIDS virus -- a finding that may lead to a vaccine that will finally work against the killer microbe.
The antibody, taken from a unusual patient whose body can resist the virus, recognizes and attacks the human immunodeficiency virus, unlike most of the body's defenses.
"Nothing like this has ever been seen before," Ian Wilson of The Scripps Research Institute in La Jolla, California, who led the research, said in a statement.
AIDS has killed 25 million people around the world and is projected to kill 80 million by 2010. The only real hope of fighting the incurable virus is a vaccine, but efforts so far have flopped although dozens of vaccines are being tested.
Antibodies are an important arm of the body's defenses against germs. They are usually able to recognize an invader by structures on its surface, called antigens, and can either call in help, or neutralize it themselves by pasting themselves against it.
Most vaccines in use today stimulate the production of neutralizing antibodies.
The human body makes plenty of antibodies against HIV, but the virus disguises itself with human sugars.
One antibody seems to be able to see past this ruse. Called 2G12, it was found by Austrian researchers a decade ago in a patient who seemed to resist acquired immune deficiency syndrome -- the condition caused as HIV destroys the immune system over time.
SPECIAL STRUCTURE
Writing in the journal Science, Wilson and colleagues said they had figured out how 2G12 does it.
It recognizes that while HIV is covered up with human sugars, they are not arranged in a human-like way.
The antibody does this with a special structure of its own, which Wilson and colleagues, including a team at Oxford University in Britain, have crystallized and imaged.
"The Fab (antigen recognition) arms are interlocked," said Scripps researcher Dennis Burton, who worked on the study.
"It's not the usual Y or T shape -- it's more just like a big long, capital-I shape," Burton added in a telephone interview. "That is a unique arrangement, and it is good for recognizing a cluster of shapes like sugars on a virus."
Now what needs to be done is to use the structure of the antibody as a template to design an antigen to stimulate the production of 2G12 or another antibody that will neutralize HIV, the researchers said.
Such an antibody alone will not be enough to prevent HIV infection, researchers believe. Because it affects the immune system, experts including Burton believe a vaccine will have to stimulate a second arm of the immune system -- the T-cells.
But the approach might also work for making vaccines against other germs, said Wilson. "Can we now use this to engineer antibodies with higher affinity against other antigens or clusters of antigens?" he asked.
Burton said his team would try, and would also test the antibody against tumor cells.
The antibody, taken from a unusual patient whose body can resist the virus, recognizes and attacks the human immunodeficiency virus, unlike most of the body's defenses.
"Nothing like this has ever been seen before," Ian Wilson of The Scripps Research Institute in La Jolla, California, who led the research, said in a statement.
AIDS has killed 25 million people around the world and is projected to kill 80 million by 2010. The only real hope of fighting the incurable virus is a vaccine, but efforts so far have flopped although dozens of vaccines are being tested.
Antibodies are an important arm of the body's defenses against germs. They are usually able to recognize an invader by structures on its surface, called antigens, and can either call in help, or neutralize it themselves by pasting themselves against it.
Most vaccines in use today stimulate the production of neutralizing antibodies.
The human body makes plenty of antibodies against HIV, but the virus disguises itself with human sugars.
One antibody seems to be able to see past this ruse. Called 2G12, it was found by Austrian researchers a decade ago in a patient who seemed to resist acquired immune deficiency syndrome -- the condition caused as HIV destroys the immune system over time.
SPECIAL STRUCTURE
Writing in the journal Science, Wilson and colleagues said they had figured out how 2G12 does it.
It recognizes that while HIV is covered up with human sugars, they are not arranged in a human-like way.
The antibody does this with a special structure of its own, which Wilson and colleagues, including a team at Oxford University in Britain, have crystallized and imaged.
"The Fab (antigen recognition) arms are interlocked," said Scripps researcher Dennis Burton, who worked on the study.
"It's not the usual Y or T shape -- it's more just like a big long, capital-I shape," Burton added in a telephone interview. "That is a unique arrangement, and it is good for recognizing a cluster of shapes like sugars on a virus."
Now what needs to be done is to use the structure of the antibody as a template to design an antigen to stimulate the production of 2G12 or another antibody that will neutralize HIV, the researchers said.
Such an antibody alone will not be enough to prevent HIV infection, researchers believe. Because it affects the immune system, experts including Burton believe a vaccine will have to stimulate a second arm of the immune system -- the T-cells.
But the approach might also work for making vaccines against other germs, said Wilson. "Can we now use this to engineer antibodies with higher affinity against other antigens or clusters of antigens?" he asked.
Burton said his team would try, and would also test the antibody against tumor cells.