One step closer to a multivalent vaccine against…

One step closer to a multivalent vaccine against…

With the SARS-CoV-2 responsible for covid 19, we are dealing with a constantly evolving virus whose variants evade the immune defenses that we develop after a first infection or vaccination. This possibility of escape obliges us to restimulate our immunity by administering booster vaccines, if possible adapted to the variants in circulation.

Other viruses are well known for the frequency and importance of their mutations, these are those of the flu. They infect many animals, which constitute an immense reservoir of different viral genomes, and the nature of these genomes, made up of RNA segments, facilitates their evolution, by mutation or by exchange of RNA fragments (recombination). Each year, viruses with modified antigenic characteristics can thus be put into circulation, and they can infect millions of individuals who are nevertheless already immunized against strains that appeared previously. The protection of populations thus requires an annual adaptation of the composition of the vaccines, carried out before the virus circulation season by WHO experts. The alternation of these seasons between the northern and southern hemisphere makes it possible to identify the viral types which will probably be responsible for the next epidemic and to include them in the vaccines.

For years, research has been carried out to define and develop an influenza vaccine whose formula would be constant, capable of protecting against all the influenza viruses responsible for epidemics in humans, and which it might not be necessary to re-administer every year.

In a news item of December 16, 2020, we presented the first encouraging results obtained with a vaccine candidate containing a modified surface protein of the virus, hemagglutinin (HA), which induced an immune response against a part of this protein, conserved in different viruses. However, the antibodies produced in the trial participants only recognized hemagglutinins belonging to the same antigenic group, indicating the need to further extend the composition of the vaccine to other antigens.

This extension of the composition of a vaccine to all subtypes of the same virus has become possible with messenger RNA technology. It is indeed relatively easy to synthesize populations of these molecules encoding slightly different protein fragments, so as to present the immune system with all the known variations of these antigens. This is what Scott Hensley and his team did to create a vaccine presenting the antigens of 20 influenza A and B virus subtypes. The mice and ferrets to which the vaccine was administered produced antibodies against all the antigens present in the formula. They were protected against infections by the corresponding viruses but also against viruses belonging to other subtypes.

A polyvalent influenza vaccine may not yet be forthcoming, but this work provides proof of concept: an RNA vaccine can provide protection against viruses with large antigenic variations by inducing a response simultaneous to multiple antigens.

Beyond the question of the real effectiveness of such vaccines, which has not yet been answered and which it may be difficult to demonstrate in humans if the viruses against which they are developed do not circulate effectively , will arise that of their acceptability, whereas they are intended to protect against infections which remain hypothetical.


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