The annual flu shot may soon be a thing of the past, thanks to a group of scientists who have identified a key vulnerability in the influenza virus that opens the door to a universal vaccine.
The research, published in the journal Nature, found that antibodies that target a previously overlooked area of the constantly mutating virus may also be able to recognize and neutralize a wide range of other strains of influenza. The versatile antibodies found in this area — referred to by the team as the anchor — are relatively common in the human body, making them ideal for vaccine use.
“It’s always very exciting to discover a new site of vulnerability on a virus because it paves the way for rational vaccine design,” said Andrew Ward, co-senior author of the study and professor of integrative structural and computational biology at Scripps Research in San Diego, Calif. “It also demonstrates that despite all the years and effort of influenza vaccine research there are still new things to discover.”
Seasonal influenza causes around one billion infections and up to 650,000 deaths worldwide every year, according to Infection Prevention and Control Canada. Combined with pneumonia, the virus ranks as one of the top 10 causes of death in Canada, resulting in an estimated 12,200 hospitalizations and 3,500 deaths annually.
Influenza vaccines generally work by inducing the immune system to produce antibodies that target the head of a protein, known as hemagglutinin (HA), that extends outward from the surface of the virus. Although the head makes for an accessible target, it is also one of the most variable parts of the virus and yearly mutations create the need for constantly changing vaccines.
“By identifying sites of vulnerability to antibodies that are shared by large numbers of variant influenza strains we can design vaccines that are less affected by viral mutations,” said Patrick Wilson, co-senior author of the study and a professor of pediatrics at Weill Cornell Medicine in New York. “The anchor antibodies we describe bind to such a site. The antibodies themselves can also be developed as drugs with broad therapeutic applications.”
The team zeroed in on this anchor area of the HA protein by characterizing 358 different antibodies found in the blood of people who had either received a flu shot, were in a trial for an experimental flu vaccine or had been naturally infected by the virus. A group of antibodies that were bound to the bottom of the less-variable stalk region of the HA quickly stood out.
In this anchor area, scientists found 50 different antibodies — from a total of 21 different people — that were capable of recognizing a range of H1 influenza viruses that account for many strains of the flu. In tests on mice, these antibodies were able to prevent infection from three different H1 influenza viruses.
“In order to increase our protection to these highly mutating viruses, we need to have as many tools as we can,” said Julianna Han, a staff scientist in Ward’s lab. “This discovery adds one more highly potent target to our repertoire.”
The team is planning follow-up research on how to most effectively design a universal vaccine that targets the HA anchor of multiple influenza strains, said Jenna Guthmiller, a post-doctoral fellow at the University of Chicago. “The human immune system already has the ability to make antibodies to this epitope, so it’s just a matter of applying modern protein engineering methods to make a vaccine that can induce those antibodies in sufficient numbers.”
Dave Yasvinski is a writer with Healthing.ca