Scientists create artificial protein to mimic part of HIV outer coat

A new artificial protein that mimics a site on the outer coat of HIV could lead to viral neutralization, according to a study recently published in Proceedings of the National Academy of Sciences.

Scientists with Duke Medicine and the Memorial Sloan-Kettering Cancer Center developed the artificial protein which is coupled with a sugar molecule and may allow antibodies to bind to neutralize various HIV strains. The new protein could lead to a new strategy for the development of vaccines that elicit broadly neutralizing antibodies against HIV.

"This new protein will allow the testing of a major hypothesis for why broadly neutralizing antibodies are so difficult to produce -- that of competition between desired and undesired antibody responses," Barton Haynes, the senior author of the study, said. "By immunizing with a vaccine that primarily has the desired target for the immune system, we will be able to see if the immune system is now free to make this type of response."

HIV uses multiple strategies to camouflage vulnerable envelope regions on the outer coat of the virus. Recent research demonstrated that the human immune system prefers not to target the vulnerable sites, but instead aims for outer coat sites that do not result in the production of protective antibodies.

The research team developed a glycopeptide, an artificial protein with sugars attached, that was meant to readily bind to broadly neutralizing antibodies. The protein may trigger the immune system to create antibodies to neutralize the HIV virus.

"It's by presenting the correct target for a neutralizing antibody, yet masking the dominant undesired target, that a vaccine can provide a fair chance for neutralizing antibodies to develop," S. Munir Alam, the study's lead author, said. "As in the case of our designed glycopeptide, if we start with a vaccine, to which not only the broadly neutralizing antibodies bind well, but also the receptors on naive B cells, we hope to optimize the chance that the induced antibodies will go down the right path."

Alam said that additional studies are ongoing, including attempts to create a crystal structure of the protein bound to the neutralizing antibody and tests of the protein in animal models.