US scientists create multipurpose flu vaccine

Using technology from the most effective Covid-19 vaccines developed to date, scientists in the United States have created a multipurpose immunization against the flu. It covers all the major disease virus subtypes—something no currently available vaccine can do.

The approach, for now, has only been tested in laboratory animals and there is still a long way to go before it can be approved for use in humans. Even so, the results, which have just come out in the specialized journal Science, suggest that it is possible to circumvent one of the major limitations of current flu vaccines. The big problem with the methods most used today is precisely the need to “bet” on a small number of subtypes of the disease when creating immunization, without knowing whether they will be the most relevant in terms of the risk they bring to the population.

Coordinated by Claudia Arevalo and Scott Hensley, from the University of Pennsylvania, the work is based on mRNA vaccines (messenger RNA), a DNA “cousin” molecule that is also used in most of the immunizations against Covid-19 that have been applied in Brazil.

In this approach, specialists assemble an mRNA molecule that contains the recipe for the production of one of the proteins that make up the disease virus. Upon reaching the patient’s body, this stretch of mRNA is “read” by the cells, which begin to produce the viral proteins.

With this, the body’s immune (defence) system recognizes that it is facing foreign substances and learns, among other things, to produce antibodies, molecules capable of attacking such substances. Thus, when the real virus comes into contact with the vaccinated person, the immune system already has a specific arsenal against the enemy, which prevents infection or greatly minimizes its effects.

The same logic applies to the older flu vaccines that are widely used today. The difference is that, in them, the ingredient that helps to “train” the immune system is not the mRNA, but the disease virus itself, grown in chicken eggs and inactivated with detergent. The issue is that, with this approach, the vaccines include in their formulation inactivated viruses of a maximum of four strains (varieties) of the flu causes.

However, there is a wide variety of flu strains, which are part of no less than 20 different lineages of the so-called influenza A and B viruses, the most important to affect human beings. In theory, a universal flu vaccine could try to identify common elements among all these viruses to create a formulation that prevents the action of any of them. In practice, however, no one has yet figured out how to do this.

The University of Pennsylvania team, in their study in Science, decided to take an approach that other researchers call “brute force”: using mRNA molecules from representatives of all 20 strains of influenza A and B at once. For this, they chose the mRNAs that correspond to the “recipe” of hemagglutinin, a protein on the surface of influenza viruses that they use to bind to the membrane of human cells. That is, it is a good target if the idea is to prevent the initial steps of the infection.

Laboratory tests with mice and ferrets (animals often used in studies of respiratory diseases) have shown that the approach can work. The animals were able to produce good levels of antibodies against viruses from all 20 strains and did not get sick when they were directly inoculated with flu strains. The protective effect was also extended to strains whose genetic material had not been included in the vaccine formulation, although in these cases the animals had mild symptoms of the disease.

Alyson Kelvin and Darryl Falzarano, researchers from the University of Saskatchewan (Canada) who commented on the study at the request of Science, claim that the polyvalent mRNA vaccine could bring better results than current immunizations against the flu because it even seems to be able to completely block infection in the lungs, as indicated by data in ferrets.

According to them, a possible concern to be analyzed is the fact that such a vaccine would involve the use of genetic material from viruses that are not currently circulating among humans. On the one hand, this could prevent the emergence of new flu pandemics, but it also has the potential to direct the evolution of new strains of the disease.

“But this scenario seems unlikely, because the multivalent vaccine, in this study, is associated with the prevention of infection and virus replication. These results suggest that, very likely, this vaccine would decrease the potential for the appearance of new viral strains”, they write . In any case, further studies are needed to better understand the potential and limitations of the approach, say the pair.