New Artificial Protein Could Represent New Strategy in HIV Vaccine Development

Researchers created an artificial protein combined with a sugar molecule that is capable of mimicking a key site on the outer coat of HIV where antibodies bind to neutralize a variety of HIV strains.

Published in the Proceedings of the National Academy of Sciences, the findings offer "a potential new strategy in vaccine development to elicit the broadly neutralizing antibodies considered essential for long-lasting protection from the ever-changing HIV virus," according to the press release outlining the discovery.

Designed by Duke and Harvard University scientists, the new protein was made by researchers at Memorial Sloan Kettering Cancer Center in New York.

"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," explained senior author Dr. Barton Haynes, director of the Duke Human Vaccine Institute. "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."

In developing the protein, the researchers were building upon a growing body of research outlining how the HIV virus is able to overcome possible vaccine candidates as well as how the system reacts to the pathogen.

"The targets of protective antibodies are vulnerable regions of the outer coat of the virus, also called the viral envelope. HIV protects these vulnerable envelope regions with multiple strategies that camouflage the sites," the press release reads, adding that recent studies have "demonstrated that the human immune system prefers not to target these vulnerable sites, but instead aims at the outer coat sites that do not result in the production of protective antibodies."

Fostering the desired antibodies isn't been easy since they often have unique features that result in their being targeted by the body's immune system. As a result, less effective antibodies take over, sometimes going so far as to crowd out the preferred ones.

By constructing a glyocopeptide, an artificial protein with sugars attached, the researchers were able to overcome these challenges. The secret lies in the glyocopeptide's structure, which allows it to easily bind with the broadly neutralizing antibodies rather than the dominant ones, giving the former the chance to develop.

Another feature the researchers believe may be critical for any vaccine capable of inducing antibodies that can neutralize the HIV virus is the ability of the newly synthesized glyocopeptide to attach to the ancestors of the desired antibodies, with the possibility of triggering the receptors on B cells of the neutralizing antibodies. B cells are white blood cells responsible for producing antibodies.

"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," said lead author S. Munir Alam, a professor of medicine and pathology at Duke. "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 naïve B cells, we hope to optimize the chance that the induced antibodies will go down the right path."