Universal flu vaccine, when it arrives
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Every year, the flu vaccine prevents millions of infections, hundreds of thousands of hospitalizations and several thousand victims from the complications of the seasonal virus worldwide. Precise recent data exists only for the United States, where vaccination in the 2019-2020 season avoided 7.5 million cases, 105,000 hospitalizations and 6,300 victims.
In short, the antidote to the flu works and saves lives, but as we know it must be constantly updated. In fact, every year, the virus strains that infect humans – influenza A and B – are transformed in such a way as to at least partially evade the vaccine and our immune system. This decreases the effectiveness of vaccination, which however remains a powerful means of defense, especially for fragile subjects. New hope for developing a flu vaccine that can fight different variants year after year comes from a major study published in Proceedings of the National Academy of Sciences by an international team of experts.
Researchers have developed a drug that takes advantage of the messenger mRna technology employed today by Pfizer-BioNTech and Moderna vaccines for SARS-CoV-2 and that targets four viral proteins in particular, which tend to remain the same even across different strains. A technology, the study reads, that could guarantee us in the near future potentially more effective vaccines capable of reducing the spread and serious outcomes of a disease that kills from 290 to 650 thousand victims worldwide every season, according to the most recent WHO estimates.
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The long road to the flu without updates
Efforts to develop a vaccine that does not need updating against seasonal flu have been repeated without results since 1933, when three researchers from the Medical Research Council in the United Kingdom they discovered that the real culprit of the terrible Spagnola of 1918 was a virus and not a bacterium, as had been assumed until then.
It was precisely the more than 50 million deaths of the Great Flu that gave the impetus to scientific research, which led in 1945 to the first patented formulation of a vaccine against the flu. Since then, the flu has been updated annually to “track” the variants that emerge, based on isolated strains in southern hemisphere countries, such as Australia, where the viral season arrives earlier and runs from April to October.
WHO, assisted by all the most important global health institutions, then develops forecast models on which influenza viruses will circulate the most. But estimates are not always accurate enough, as they need to be made months in advance to ensure vaccine development and delivery times around the world. And so it happens that as the severity and the presence of more or less contagious variants vary, the effectiveness of today’s anti-flu can vary from 60 to 10% from year to year.
The joint work between the University of Pennsylvania, Icahn School of Medicine of New York and other research centers aims to create a vaccine capable of fighting various strains of influenza by targeting some specific antigens, regardless of the variants that emerge. A very different method from the way we develop them today, which is to make the virus grow and replicate in the laboratory and then inactivate it so that the body learns to recognize it, but without the risk of getting sick.
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“The goal – he explains Florian Krammervirologist at Icahn School of Medicine and co-author of the analysis – is to exploit certain viral proteins that do not change and remain essentially the same regardless of the strain of influenza that is spreading. “
The “novelty” of the messenger mRna
The technology that exploits mRna is not new, but we only got to know it well with the advent of vaccines that allowed us to calm a pandemic from which there seemed to be no way out. But how does it work? Simply put, a piece of genetic code is used to provide information about the virus to the body, which in turn produces viral proteins that are then recognized as foreign by the immune system. Thus, antibodies and memory cells are produced, making the body prepared to fight the virus once it comes into contact. The mRna molecule is not able to alter human DNA in any way and its natural instability means that it is eliminated within two days of administration.
New hope comes from preclinical trials
The group of virologists and microbiologists led by Professor Norbert Pardione of the most active and influential experts in the world in this field, has created a “cocktail” based on mRna including in the genetic material neuraminidase, nucleoprotein, matrix-2 protein and hemagglutin, all molecules responsible for adhesion viruses to the cells they infect.
The new drug was then administered in various combinations to a group of mice brought into contact with different strains of contagious influenza for humans and animals. “The results are really encouraging – note the authors – and make us think that this platform can soon be used to combat the spread of various classes of influenza viruses”.
Blood tests conducted on groups of mice, in fact, showed high levels of antibodies for all formulations of the vaccine, from that with a single segment of mRna, to that with all four proteins considered. “The complete protection was obtained for the group to which the quadrivalent dose was administered – reads the conclusions – while elevated levels of cytotoxic T lymphocytes were recorded even in the monovalent”.
This aspect is particularly interesting, because we now know with certainty how important the so-called T-killers are for a good course of the flu disease: leukocytes programmed to attack bacteria, cells that host viruses and tissues foreign to the body. “However, we had the best results in the quadrivalent group, with an involvement of T cells against the nucleoprotein, a significant production of antibodies and a strong inhibitory response against neuraminidase,” continues Krammer.
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It may take a few more years for a universal influenza vaccine developed with messenger mRna technology to come out. At that point, clinical trials will be needed to evaluate its safety and efficacy and then a long approval process by the most important regulatory agencies in the world. In the meantime, we can decide to trust vaccines that have already been subjected to these procedures: vaccination against influenza in Italy began in October and is recommended by the Ministry of Health and Aifa.
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