Wednesday, December 8, 2021
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Towards a universal influenza vaccine?

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The flu virus changes every year. The vaccine must therefore continually adapt. But new research could lead to the development of an influenza vaccine that protects against many strains. Is the universal flu vaccine coming tomorrow?

The flu is a very common viral disease that kills between 290,000 and 650,000 million people each year around the world according to the WHO. Very contagious, it is at the origin of an annual epidemic which lasts 4 months on average. Vaccination remains the most effective way to fight the flu. The virus is very mutable, it is currently necessary to be vaccinated every year for people at risk. How to have a “universal” vaccine against influenza, protection which would remain effective whatever the mutations of the virus? Several teams are working on such a project and two studies offer real hope.

Variations of the influenza virus

The influenza virus is constantly evolving, which implies the development of a new vaccine each year. Currently, seasonal influenza vaccines induce the production of antibodies directed against regions of hemagglutinin (HA), which makes up about 40% of the surface glycoproteins of the virus. It is the rapid changes in this protein that make the development of new vaccines mandatory every year.

Basically, an international biomonitoring network collects samples of circulating viruses and transmits them to the reference laboratories of the World Health Organization. When a new strain is identified, experts predict which strain of the virus will be prevalent in the next season.

The virus of the year is then sent to drug companies to develop a vaccine that can fight it. This process involves preparing the vaccine strain (or vaccine virus, the weakened version of the virus) and multiplying it in chicken eggs. The production and development process remains relatively long, and the main risk is that a new mutation will emerge while a vaccine is being developed. These strains undergo a slight mutation every year, and change dramatically every 30 years or so.

Finally, the protection offered by the vaccine is not total. WHO estimates that on average, the vaccine prevents about 60% of infections in healthy adults between the ages of 18 and 64. Which is roughly halving the risk of contracting the flu alone.

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Advances in research towards universal protection against influenza

Researchers at the American Institute of Allergy and Infectious Diseases have used an innovative technique to obtain a universal broad-spectrum vaccine3.

Unlike traditional vaccines that target the head of hemagglutinin, they have targeted the base of this protein, which is much more stable. The vaccination schedule was carried out in two stages according to the technique of “prime-boost” which is based on the use of a duo of vaccines, carried out in two stages:

  • First, the injection of a piece of DNA encoding the HA protein (the hemagglutinin stem) of the 1999 virus was used to activate the immune system;
  • Secondly, the administration of a seasonal influenza vaccine (from 2006-2007) or a vaccine created from an adenovirus encoding the HA protein makes it possible to restart the immune system; 
  • Tested in mice, ferrets and monkeys, this strategy stimulated antibody synthesis not only against strains after 1999 but also against an influenza strain dating from 1934. Additionally, although the vaccine was designed to From H1 subtypes of A viruses, it has been shown to be effective against avian influenza.

Flu shot: when to get the influenza vaccine?

In another series of experiments, researchers wanted to assess the protection of this vaccine against lethal doses of influenza virus. Three weeks after the injection, 20 mice were exposed to lethal doses of the influenza virus of 1934. Result: 80% survived (compared to none of those who had not received both injections). “We are very excited about these results. The prime-boost approach makes it possible to envisage a vaccination against influenza similar to that against hepatitis, in which the vaccination is started in early childhood and then immunity is stimulated through to additional injections in adulthood,” says Dr. Nabel, study leader.

Another study5 reports the case of individuals vaccinated against different influenza viruses of the H1 and H3 subtypes, who developed antibodies against other subtypes including H5, which has the dreaded avian influenza in its ranks. These antibodies targeted hemagglutinin (HA), but again a more stable part of the protein.

Four of these antibodies, tested in vivo in mice, protected them against different subtypes. Although these antibodies protect mice against influenza viruses of porcine origin H1N1 or several H5N1 viruses, the authors note that further studies will be necessary: ​​on the one hand to determine whether these individuals produce enough antibodies to protect them against different influenza subtypes and on the other hand, to know how vaccination can, if necessary, promote this production of antibodies.

Effective immune cells against all viruses?

In a study published in the scientific journal Nature Immunology, Australian researchers claim to have discovered immune cells capable of fighting all influenza viruses. Already present in some organisms, CD8 T lymphocytes could, according to the study authors, be used to develop a universal vaccine. 

While these three studies bear witness to the dynamism of research in this quest for a universal influenza vaccine, they cannot represent all of the avenues considered. Thus, certain teams are interested in other parts of the influenza virus (in particular an M2 protein also present on the surface of the virus 6) or in the development of new adjuvants. Remember that the stakes are high: influenza is responsible for 250,000 to 500,000 deaths each year.

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