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Scientists have used mRNA technology to create a vaccine that can protect against 20 types of influenza.
A flu shot against all 20 known subtypes of influenza A and B virus protected mice and ferrets against several strains of flu, according to data published yesterday in Science.
The two-dose vaccine uses the same mRNA technology used to make COVID-19 vaccines, only in this case it delivers small particles containing the instructions for making the haemagglutinin proteins found on the surface of the influenza virus into cells. The cells start manufacturing these proteins, triggering an immune response.
The vaccine elicited high antibody levels that remained steady for at least four months and animals exposed to several strains of flu were protected from severe disease or death, despite evidence of viral infection in their lungs.
As well as haemagglutinin proteins, flu viruses have another surface protein called neuraminidase. Together, these form the “H” and “N” designations given to different subtypes of influenza, e.g. H5N1 or H1N1. Both proteins can mutate, but haemagglutinin is especially prone to mutations – flu mutates even faster than coronaviruses.
Thus, seasonal flu vaccines are developed using scientists’ best guess about what the predominant circulating strains will be during the subsequent flu season. Though very effective at reducing hospitalisations and deaths from flu at a population level, influenza’s rapid mutation rate makes keeping up with it difficult. The seasonal vaccine also offers little protection against potential pandemic strains.
The new vaccine, however, offers such broad protection against a range of flu strains that it could even protect against future pandemic strains of influenza.
The world has already experienced several flu pandemics within the past hundred years or so. During the 1918 flu pandemic, the H1N1 strain infected about 500 million people (a third of the world’s population at the time) and is estimated to have killed at least 50 million.
Since then, there have been three pandemics – H2N2 in 1956, H3N2 in 1968 and H1N1 in 2009.
The threat of another flu pandemic is high, especially from two strains of bird flu –- H5N1 and H7N9. These have been a source of deep concern in recent years as mutations meant that they were able to spillover from poultry into people. In the case of H7N9, there has also been limited spread between humans, although fortunately this has not been sustained.
This year has seen a record outbreak of the highly contagious H5N1 strain in poultry, with 48 million birds culled in the UK and EU alone, partly because of concerns that it could spread to people.
Seasonal flu vaccines are currently produced by growing influenza viruses in chicken eggs and then deactivating them. Creating vaccines this way can incorporate a maximum of four viral antigens that trigger an immune response, which isn’t enough to induce broad immune responses.
The hunt for a universal flu vaccine has therefore been on for decades, with some approaches aiming at the stalk of the haemagglutinin protein which attaches it to the virus, as this is less prone to mutation. However, while this approach can trigger broadly reactive antibodies and cross-protection across strains, the immune response is not especially strong.
In the new study, Claudia Arevalo and colleagues, at the University of Pennsylvania, Philadelphia, US, included mRNAs that encode haemagglutinin proteins representing every type of flu virus known to be a threat to people. The vaccine also triggered antibodies to the haemagglutinin stalk.
“Current mRNA vaccine platforms allow the inclusion of many mRNAs that will induce many different proteins, giving a multivalency and breadth of response that was not easy to achieve with protein platforms in the past,” said Raúl Ortiz de Lejarazu y Leonardo, Professor of Microbiology and director emeritus of the National Influenza Centre in Valladolid, Spain.
As promising as this research is, “there is a long, sometimes insurmountable, way to go from the animal model to humans,” he warned.
What’s more, the “regulatory and approval pathway of such a vaccine that targets viruses of pandemic potential but that are not currently in human circulation” is unlikely to be straightforward, said Alyson Kelvin and Darryl Falzarano at the University of Saskatchewan, Canada, writing in an accompanying commentary in Science. It is therefore important not to wait until the next flu pandemic before starting these discussions, they added.
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