Researchers at Scripps Research, University of Chicago, and Icahn School of Medicine, Mount Sinai identified an important new weakness in influenza virus. This discovery has made progress in the search for a universal vaccine. The team reported that antibodies against the long-ignored virus section, known as the anchor, could recognize many flu strains even though the virus evolves from year to year.
“It’s always very exciting to discover a new site of vulnerability on a virus because it paves the way for rational vaccine design,” says co-senior author Andrew Ward, PhD, professor of Integrative Structural and Computational Biology at Scripps Research. “It also demonstrates that despite all the years and effort of influenza vaccine research there are still new things to discover.”
Patrick Wilson, MD, co-senior author of the study, said that by identifying areas of vulnerability to antibodies shared by many variant influenza strains, we can design vaccines less affected by virus mutations. He was previously at the University of Chicago and was recently recruited to Weill Cornell Medicine to be a professor of pediatrics and scientist in the Gale and Ira Drukier Institute for Children’s Health. “The anchor antibodies we describe bind to such a site. The antibodies themselves can also be developed as drugs with broad therapeutic applications.”
An average year of influenza causes more than 20,000,000 deaths in the United States. Vaccines for influenza usually coax the immune systems to produce antibodies that recognize the head hemagglutinin (HA) protein. This is a protein that extends from the surface flu virus. It is one of the most easily accessible areas of HA. Unfortunately, it can also be one of the most unpredictable. The head of HA is susceptible to mutations, so new vaccines are needed.
Researchers have created experimental influenza vaccines that are more universal. This encourages the body to make antibodies against the stalk region of HA which is less variable. It acts like a stem, between the influenza virion (the influenza head) and the stalk region of HA. Some of these universal flu vaccines have already been tested in clinical trials.
A new study by a team of scientists revealed 358 antibodies in blood samples from people who were either given a seasonal flu vaccine, had participated in a Phase I trial for an experimental universal influenza vaccine or had been naturally infected.
Participants had antibodies that recognized the stalk or HA head. A group of new antibodies was found to be distinct. They bound to the stalk’s bottom, where each HA molecule attaches to the membrane of flu virion.
Julianna Han, a Ward staff scientist, and Jenna Guthmiller (a postdoctoral fellow from the University of Chicago) were the co-first authors of this manuscript. They named the section of HA “anchor” and began to study it more. From a total 21 people, they identified 50 antibodies to the HA Anchor. They discovered that the antibodies recognized many H1 influenza viruses. These viruses are responsible for many seasonal flu strains. In laboratory tests, some antibodies were also capable of recognizing pandemic H2 strains and H5 influenza viruses. The antibodies also protected mice against three H1 influenza viruses.
Han says, “In order to increase our protection to these highly mutating viruses, we need to have as many tools as we can. This discovery adds another highly potent target to our arsenal.”
Guthmiller adds that the human immune system is already capable of making antibodies to this epitope. It’s now a matter to use modern protein engineering techniques to create a vaccine that can induce those antibodies in sufficient quantities.
Researchers believe that future iterations could be more deliberate in generating anchor antibodies. Scientists who have been developing universal vaccines had not considered whether the anchor region of a stem was a target. A universal vaccine against influenza should produce antibodies that are immune to multiple parts of the virus, such as the stalk and the HA anchor. This will increase protection from evolving viruses.
Future studies are being planned by the researchers to determine how to create a vaccine that targets the HA anchor in different strains of influenza.