Redesigned Antibody 4 Times Stronger in Neutralizing HIV

Specialty Pharmacy Times, July/August 2015, Volume 6, Issue 4

Redesigning an antibody may lead to a vaccine that neutralizes HIV, according to the results of a recent study. The study, published online in The Journal of Clinical Investigation, indicates that computer-redesigned antibodies may accelerate the search for an effective HIV therapy, which has thus far eluded researchers.

“There’s a consensus [in the HIV field] that the vaccine that works is going to be a designed one,” said co-lead researcher James Crowe Jr, MD, in a press release.

The researchers used a “parent” antibody isolated from HIV-infected blood that strongly neutralized HIV in laboratory tests. The researchers then used the Rosetta computer program to predict the structure of a protein from its amino acid sequence in order to redesign the antibody.

In changing a single amino acid, the stability of the antibody increased when it bound to the HIV envelope protein. By improving thermodynamic stability, the antibody grew more rigid and was better suited to fit the HIV protein like “a lock and key,” the study noted.

“By changing a single amino acid, we made it 4 times more potent, 4 times stronger, and it also started killing even more HIV strains than the parent antibody,” Dr. Crowe said. The isolated antibody was subsequently produced in great quantities from just a single clone of immune cells. The redesigned antibody is currently undergoing clinical trials.

“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,” he added.