Scientists from Scripps Research, the University of Chicago and the Icahn School of Medicine at Mount Sinai, in the United States, identified a new ‘Achilles heel’ of the flu virus, which represents an advance in the search for a universal vaccine against this disease.
Antibodies against a long-ignored section of the virus, which the team called an “anchor,” have the potential to recognize a wide variety of flu strains, even when the virus mutates from year to year, as explained in an article published this Thursday in the magazine ‘Nature‘.
“It is always very exciting to discover a new vulnerability in a virus because it paves the way for vaccine design. It also shows that despite all the years and research efforts on the flu vaccine, there are still new things to discover“Explains one of the co-authors of the research, Andrew Ward, professor of Structural and Computational Integrative Biology at Scripps Research.
By identifying sites of vulnerability to antibodies that are shared by a large number of variant influenza strains vaccines can be designed that “are less affected by viral mutations”explains another of the authors, Dr. Patrick Wilson.
The ‘anchor’ antibodies they describe bind to that site. “Antibodies themselves can also develop as drugs with wide therapeutic applications “, details Wilson.
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Flu vaccines typically induce the immune system to generate antibodies that recognize the head of hemagglutinin (HA), a protein that extends outward from the surface of the flu virus. The head is the most accessible region of HA, which makes it a good target for the immune system; unfortunately, it is also one of the most variable. From one year to the next, the HA head often mutates, necessitating new vaccines.
The researchers designed experimental flu vaccines to be more universal, stimulating the body to create antibodies against the HA stem region, less variable, that extends like a stem between the influenza virion and the HA head. Some of these universal flu vaccines are currently in early clinical trials.
In this new study, the team of scientists characterized 358 different antibodies present in the blood of people Who had been given a seasonal flu vaccine, who were in a phase I trial of an experimental universal flu vaccine, or who were naturally infected with the flu.
Many of the antibodies present in the participants’ blood were antibodies that it was already known that they recognized the head or stem of HA. However, a group of new antibodies stood out: the antibodies were attached to the bottom of the stem, near where each HA molecule binds to the membrane of the influenza virion.
They named this section of the HA the anchor, and began to study it further. Total, scientists identified 50 different antibodies against the HA anchor, from a total of 21 individuals.
They found that the antibodies recognized a variety of H1 flu viruses, which represent many strains of seasonal flu. Some of the antibodies were also able to recognize the pandemic H2 and H5 strains of influenza in laboratory tests. And in mice, the antibodies successfully protected against infection by three different H1 flu viruses.
“To increase our protection against these highly mutant viruses, we need to have as many tools as we can. This discovery adds a more highly potent target to our repertoire, ”the authors point out.
These antibodies seem to be quite common in people and belong to a class of antibodies that anyone’s body can make. an important consideration when designing a vaccine that stimulates its development.
“The human immune system already has the ability to make antibodies against this epitope, so it is only a matter of applying modern protein engineering methods to make a vaccine that can induce these antibodies in sufficient quantities,” they add in this regard.
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The researchers say future improved iterations of a universal vaccine could be aimed at generating anchor antibodies. Until now, scientists designing universal vaccines had not paid attention to including the stem anchoring region as a target. Ideally, a universal flu vaccine would elicit antibodies against multiple sections of the virus (such as the HA anchor and stem) to increase protection against evolving viruses.
The researchers are planning future studies on how to design a vaccine that more directly targets the HA anchor of different strains of flu. (Europa Press)
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