Computer-designed antibodies to help fight HIV

Brett Smith for redOrbit.com – Your Universe Online
Thus far, nature has not developed a way for humans to battle the human immunodeficiency virus (HIV), so researchers at Vanderbilt University have decided to “cheat” nature and use a sophisticated computer program called Rosetta in order to design new weapons in the battle against AIDS.
According to a new report in Journal of Clinical Investigation, Vanderbilt researchers have successfully leveraged Rosetta to engineer an antibody capable of taking down more strains of HIV than any known natural antibody can.
“There’s a consensus (in the HIV field) that the vaccine that works is going to be a designed one,” said Dr. James Crowe Jr., director of the Vanderbilt Vaccine Center, in a press release.
In the study, Vanderbilt researchers, in collaboration with scientists from The Scripps Research Institute in California, pulled an antibody from the blood of an HIV-infected person that appeared to already be highly effective in combating HIV.
Modifying the structure of an antibody
The team then used Rosetta to figure out the structure of the antibody’s effective protein based on sequencing of the antibody’s amino acids. The team then modified a single amino acid to boost the stability of the antibody when it attached to HIV – making it better able to grab onto HIV and destroy it.
“By changing a single amino acid, we made it four times more potent, four times stronger, and it also started killing even more HIV strains than the parent antibody,” Crowe said.
The breakthrough was made possible by past research from Scripps scientists who reported the structure of HIV’s envelope protein using crystallography and cryo-electron microscopy.
“Now we know what it looks like,” Crowe said. “We can better understand how to target it.”
Scripps researchers published a paper that found that “computational protein design” could be used to stimulate the body into creating antibodies of respiratory syncytial virus (RSV), a virus that causes respiratory infections in children.
“That was the first paper in which people agreed that computer design of a vaccine worked,” Crowe said.
The Vanderbilt researcher added “if computational design … can predict how viruses evolve in the future, we could potentially design antibodies and vaccines for viruses before they occur in nature.”
The study team said they are currently working together to use Rosetta for modeling interactions between viruses and the immune system.
“You couldn’t have this type of biomedical research,” Crowe said, “without that playful, curious aesthetic sense that you get with the Rosetta ‘community.’”
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