Reacción a "Reactions to preliminary results of a new universal flu vaccine prototype"

Science today publishes a paper presenting preclinical trials in mice and ferrets of an 'icosavalent' mRNA vaccine against influenza. This is the first high-impact publication to present a successful strategy for a "universal" mRNA-based vaccine against influenza. The formulation includes modified RNAs formulated into lipid nanoparticles, the same technology used by Moderna in the development of the widely distributed SARS-CoV-2 vaccines.  

The vaccine includes the 18 known haemagglutinin spicule types of influenza A viruses (H1-H18) plus two for influenza B viruses. For reference, the tri- or tetravalent influenza vaccine we are currently using contains one A/H1, one A/H3 and one or two B viruses. The seasonal influenza A viruses circulating in the human population are only H1N1 and H3N2. Why include other H antigenic types in the vaccine? Firstly, A viruses are zoonotic, and although the other types do not circulate in the human population, they do circulate in other animals, such as H5 H7 and H9 in birds. This implies that new pandemic viruses can emerge if one of these types engages in "antigenic jumping" by generating a new A virus that combines the genes of animal viruses with those of viruses circulating in humans. This is what happened in 2009, 1968 (Hong Kong flu), 1957 (Asian flu) and in the terrible 1918 pandemic that killed at least 50,000,000 people. 

This type of vaccine would therefore prevent, in addition to seasonal influenza, the spread of avian influenza in humans, which has a mortality rate of around 30%, and possible new emerging pandemic viruses. Most importantly, the authors of the study show that their cocktail generates antibodies to low-variable regions of the HA spicule, which are found in the structure of the 'stem'. The enormous mutational capacity of influenza viruses means that the virus "changes its face" from one year to the next. In other words, even if we have built up immunity to the previous winter's flu, this winter our antibodies will no longer recognise the new virus. This "antigenic drift" is similar to what happens with the sublineages of the SARS-CoV-2 omicron variant: as soon as the virus changes antigens, our immune memory no longer recognises it and we can be reinfected with the new variant.  

We have known for a long time that the influenza virus does this much faster than the coronavirus and this forces us to reformulate the vaccine every year according to the data that an international epidemiological surveillance service handles to predict what will be the presumably most effective vaccine composition for the winter season. But all that chameleon-like ability of the virus is in the "head" of the HA spicule of the virus. If we can neutralise the invariant region of the stem, we would have a "universal" vaccine, a weapon against the virus's ability to vary. The authors of this study found in their preclinical trials that using this strategy, experimental animals develop neutralising antibodies to the stem, as well as a wide range of antibodies to the 20 different "heads" of the virus' haemagglutinin.  

In short, the strategy shows good protection in experimental animals against infection, generating antibodies against all types, something that would be very difficult to achieve with conventional vaccines, and protecting the animals against infection by several types of H1N1. It appears that the presentation of the antigen to our immune system is much more effective in mRNA-based formulations, which force our cells to produce the antigen in situ, than in classical formulations based on direct inoculation of the antigen. Thanks to the technological development forced by the emergency situation created by covid-19, the formulation of vaccines and other mRNA-based drugs is entering a golden age that may lead to a revolution in the prevention and treatment of infectious diseases and other pathologies.