The findings suggest that computer-redesigned antibodies may speed the search for an effective therapy or vaccine for a virus that so far has eluded all attempts to eradicate it.
“There’s a consensus (in the HIV field) that the vaccine that works is going to be a designed one,” said James Crowe, from the Vanderbilt University Vaccine Centre who led the work.
Working with colleagues at The Scripps Research Institute in California, the researchers began with a “parent” antibody isolated from the blood of an HIV-infected person that was a strong “neutraliser” of HIV in laboratory tests.
The researchers then used the Rosetta computer programme, which can predict the structure of a protein from its amino acid sequence, to “redesign” the antibody.
By changing a single amino acid, they were able to increase the stability of the antibody when it bound to HIV’s envelope protein.
The researchers did not change the interface between the antibody and the virus. Rather, by increasing its thermodynamic stability, the antibody became more rigid and better able to fit the HIV protein like a lock and key.
“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,” said Crowe.
The original, isolated antibody is now being produced in great quantities from a single clone of immune cells, and thus is a “monoclonal” antibody.
It currently is being tested in clinical trials. Crowe said the redesigned antibody could be added to the study as a second-generation version.
The field of redesigning antibodies has grown quickly out of the need to treat and prevent debilitating and often-fatal viral infections, and from technological advances that have made it possible to “see” and strengthen the interactions between virus and virus-killing antibodies.
HIV evolves every day, or alters the envelope protein on its surface to evade immune detection, researchers said.
The research was published in The Journal of Clinical Investigation.
PTI