What will be the future of mRna-based influenza vaccines?

Moderna’s mRna-1010 experimental flu vaccine is quadrivalent in the sense that it targets four strains of influenza: A/H1N1, A/H3N2, B/Yamagata and B/Victoria, selected according to the recommendations of the World Health Organization (WHO). Now, listening to Moderna’s claims, the results of an ongoing clinical trial, just presented, would be “a major step forward in the development of mRNA-based flu vaccines”. This is a study involving 6,102 adults in Argentina, Australia, Colombia, Panama and the Philippines during the Southern Hemisphere flu season.

Participants received either the mRNA-1010 vaccine or a single dose of a licensed flu vaccine. In reality, as demonstrated by the stock market loss of the American company, things are not exactly as announced, and the results are mediocre at best. The new RNA vaccine generated an immune response against influenza A strains equal to or greater than that of already licensed vaccines, but it fell short of already approved vaccines against influenza B strains. Compared to vaccines such as Fluzone of Sanofi, moreover, in the elderly the seroconversion figure – ie the effectiveness of the vaccine in terms of induced antibody production – appears lower. It is also not entirely clear whether these data were obtained after one or two doses of RNA vaccine, compared to a single dose of conventional vaccine.

Finally, if we look at the side effectsModerna said 70% of mRna-1010 recipients reported adverse reactions such as headache, bloating and fatigue, compared to 48% in the other group, treated with the traditional product. Now, it may well be true, as stated by Moderna and the other companies involved in the development of RNA vaccines against the flu, that the ability to obtain customized annual vaccines more quickly with messenger RNA technology brings the advantage of being able to better track the seasonal variants that are more likely to be the basis of a new annual flu wave. Furthermore, it is true that the possibility of combining many different RNAs allows the production of single vaccines against different respiratory agents, thus simplifying the vaccination campaign and decreasing its costs.

However, these are points which at present still have to be proven, as opposed to the newly arrived clinical data; consequently, in the current state of knowledge it cannot be taken for granted that, in the case of influenza, it will be possible to replicate the success that RNA vaccines have had in controlling SARS-CoV-2 and the more nefarious results of Covid -19. To find out what the real utility of RNA technology is with regard to the flu virus, we will have to wait for more data, which will come both from Moderna (larger trials are underway) and from its competitors, such as Pfizer/BionTech, Glaxo/CureVac and Sanofi/TranslateBio. In particular, as regards the products of other companies, very different results could also be obtainedas already happened during the Sars-Cov-2 pandemic, due to the differences both in the modifications and sequence of the RNA used, and in the excipients used to improve the stability and pharmacological properties of the different vaccines.

The lesson to be learned, as always, is the same: data rules, and success against a certain pathogen obtained using a certain technology is no guarantee with regard to other pathogens, mainly due to the different antigenic properties of viruses and their specific biology. The new studies on RNA products against the flu and other infectious diseases are welcome; but before assuming that you have “the world’s best weapon” in your hands, keep in mind that immunology and virology are complex subjectsand that there is still a lot, a lot to learn.