A new strategy for a universal, long-lasting flu vaccine

The vaccines They train our body to prevent diseases before they even start. To achieve this it is necessary to introduce an antigen into the body, which mimics an infection and prepares the simmune system in order to respond. The antigen acts like a silhouette of a key: it gives the immune system the profile it needs to enter the pathogen and destroy it. Our immune system can confront invaders it knows and vaccines give it the keys to identify those it doesn’t know.

But there are two problems: the immune system must update itself frequently to face new viruses and these mutate. Therefore, it is also necessary to update vaccines with certain periodicity. Is there a possibility of a universal and long-lasting vaccine?

That’s what a team of scientists at Duke University led by Nicholas Heaton asked themselves. The answer is a study published in Translational Medicine that has opened a new avenue in the attack on influenza viruses (flu) by creating a vaccine that It stimulates the immune system to attack a portion of the virus surface that is less variable.

This new vaccine approach is part of a five-year effort to develop a universal flu vaccine, a more durable and capable of attacking all versions of the virus.

Influenza strains are named by a short code, for example H5N1, which describes which two proteins the virus has on its surface. Knowing this, it is possible to identify the key that would allow the antigen to identify the virus. The H (sometimes HA) is hemagglutinin, a lollipop-shaped protein that binds to a receptor on a human cell, the first step in getting the virus into the cell. N, for its part, is neuraminidase, a second protein that allows a newly created virus to escape from the host cell and infect other cells.

“ANDIn the virus particle, there is five to ten times more hemagglutinin than neuraminidase “If we were drawing your blood to see if you were likely to be protected against a flu strain, we would measure what your antibodies to hemagglutinin do as the best metric of what’s likely to happen to you,” Heaton explains. “The strongest correlates of protection have to do with hemagglutinin-driven immunity.”

Vaccines teach the immune system to react to parts of the virus that have been specifically designed for the influenza strains expected to be most threatening in the upcoming flu season. The reason we need a new flu vaccine every fall isn’t because the vaccine wears out; it’s because the influenza virus is constantly changing the surface proteins that the vaccines target.

Flu vaccines (and immune systems) tend to target the “head” of hemagglutinin. But the details of that head region are also constantly changing, creating a arms race between vaccine design and viruses. But if the head changes very often, the body not so much.

And that’s where Heaton’s team aimed. “The virus has evolved so that the immune system recognizes certain characteristics in the head region,” the study notes. But these are the ways the virus can change. “That is a strategy that is exhausted.”

Using gene editing, Heaton’s team created more than 80,000 variations of the hemagglutinin protein with changes to a portion right at the top of the head domain and then tested a vaccine filled with a mix of these variations in mice and ferrets.

“Antibodies against the virus body work differently,” says Heaton. Its protective mechanism is not necessarily to block the first step of infection. They have the advantage of entering the virus and not needing to update as much. But they are missing the quick prevention part. So We asked ourselves what would happen if we could find a vaccine that gives us both. Basically our study says yes, we can do it.».

Because of the wide variety of head conformations presented to the immune system and the relative consistency of the virus “bodies,” these vaccines produced more antibodies against the hemagglutinin portion of the body in response. The new approach worked well in experiments with mice and ferrets, and may lead to flu vaccines with greater protection and less reliance on an annual injection tailored to that year’s versions of the virus. Even with vaccines, the flu kills about half a million people each year worldwide.

In laboratory and animal tests, the experimental vaccine caused the immune system to respond more strongly. This boosted the immune response to the vaccine overall and, in some cases, even enhanced antibody responses to the core region of the protein.

After one injection of the vaccine was administered in the experiments, 100% of the mice avoided illness or death from what should have been a lethal dose of flu virus. The next steps of the research will try to understand whether the same level of immunity can be achieved by presenting fewer than 80,000 hemagglutinin variants.