Discovery of a new target promises a long-lasting, universal flu vaccine

An international research effort might finally lead us to a universal, long-lasting flu vaccine.

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Influenza, or ‘the flu’, is one of the most persistent viruses that humanity has contended with throughout history. Although several vaccines against the flu have been developed and deployed year after year, the virus’ high rate of mutation means that it often bypasses our bodies’ immunity. It also leads to a huge number of influenza strains, often quite different from one another, making it hard for a single vaccine to provide immunity against all of them at the same time.

So far, we’ve been unable to develop a single, long-lasting, and broadly-acting vaccine against the flu. However, new research might change this.

Targeting the anchor

“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.”

The findings come from a combined effort of researchers at Scripps Research, University of Chicago and Icahn School of Medicine at Mount Sinai. Their work revealed a previously-unknown vulnerability of the influenza virus — a section that is very stable across time and strains (i.e. it doesn’t mutate almost at all) which the team dubs ‘the HA anchor’.

Since this anchor is common among strains and doesn’t change over time, a vaccine designed to interact with this anchor will be effective across strains and over the years, despite the virus’ propensity to mutate.

“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,” says study co-senior author Patrick Wilson, MD. “The anchor antibodies we describe bind to such a site. The antibodies themselves can also be developed as drugs with broad therapeutic applications.”

On average, influenza infects over 20 million people and leads to 20,000 deaths in the United States alone — many more worldwide. Current vaccines target an area on the virus known as the head of hemagglutinin (HA), a protein that extends outwards from its shell. Although this area is easy to reach and highly reactive, which makes it a good target for our immune system, it’s also one of the most volatile parts of the virus, changing very rapidly. It’s the mutations of the HA that make it necessary for new influenza vaccines to be developed every year.

For the study, the team looked at 358 flu antibodies from the blood of people who had been either vaccinated with a seasonal influenza vaccine, universal influenza vaccine, or had been infected with the virus.

Many of the antibodies they analyzed were already known to science and targeted known areas of the virus. However, a few stood out — they had not previously been documented and tied to a new area. This led the team to discover the anchor. In total, 50 different antibodies from 21 individuals were identified tying to this area. Mouse studies in the lab showed that these antibodies were effective against three H1 influenza viruses.

“In order to increase our protection against these highly mutating viruses, we need to have as many tools as we can,” says Julianna Han, a staff scientist in the Ward lab and one of the paper’s co-first authors. “This discovery adds one more highly potent target to our repertoire.”

“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,” adds Jenna Guthmiller, a postdoctoral fellow at the University of Chicago, the other co-first author.

The team is now working to design a vaccine that better targets the HA anchor of the virus.

The paper “Broadly neutralizing antibodies target a hemagglutinin anchor epitope” has been published in the journal Nature.

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