Researchers reveal the mechanism behind antigenic drift

A new study by researchers from the Massachusetts Institute of Technology has revealed the mechanism behind the phenomenon known as antigenic drift.

Antigenic drift occurs when pressure from the body's immune system causes a virus used in a vaccine to mutate into a slightly different form that can potentially be more infectious.

The scientists, led by Ram Sasisekharan, a professor of health sciences and biological engineering at MIT, conducted the study by examining the chain of amino acids in the viral protein hemagglutinin. They identified which amino acids were most likely to mutate into forms that would improve the viruses' capability to infect new hosts.

The knowledge acquired by Sasisekharan and his team could help influenza vaccine designers develop vaccines that do not produce fitter viruses, as the evolved strains are known.

New strains of influenza emerge constantly, leaving researchers searching for which new strains should be included in the seasonal influenza vaccine, which must be reformulated every year.

The vaccines stimulate the production of antibodies that target a section of the hemagglutinin protein known as the antigenic site. When a virus encounters antibodies it can change slightly into a form that can spread more easily to those that have not been vaccinated and can bind more tightly to the surfaces of cells in the respiratory tract of flu victims, making it more infectious.

With funding from the U.S. National Institutes of Health and the Singapore MIT Alliance for Research and Technology, Sasisekharan and his team sought to find out how this phenomenon occurs.

They examined the hemagglutinin protein using an approach called network analysis, which looks at the relationship between the individual amino acids that make up the protein. The resulting model showed that those amino acids located in the protein's antigenic region that were highly linked to those in the receptor-binding region were more likely to change affinity upon mutation. Selection pressure due to vaccination could contribute to the evolution of fitter viruses by producing better-binding hemagglutinin proteins.

“The idea that hemagglutinin can only accommodate certain mutations without losing fitness is not a new one, but what this paper gives us is a way to understand how changes in distant amino acids affect receptor binding,” David Topham, a professor at the University of Rochester School of Medicine, said.

Sasisekharan said that with knowledge of which amino acids are most likely to mutate into a more infectious form, vaccine producers could create vaccines that do not provoke mutations.

“This understanding of the relationship between the antigenic site and the receptor-binding site could be added to the current methods of vaccine selection and vaccine designs to limit drift,” Sasisekharan said.

Organizations in this story

National Institutes of Health 9000 Rockville Pike Bethesda, MD 20892

Get notified the next time we write about National Institutes of Health!