Penn Scientists develop 20-subtype mRNA flu vaccine to protect against future flu pandemics

An experimental mRNA-based vaccine against all 20 known subtypes of influenza virus provided broad protection from otherwise lethal flu strains in initial tests, and thus might serve one day as a general preventative measure against future flu pandemics, according to researchers from the Perelman School of Medicine at the University of Pennsylvania.

The "multivalent" vaccine, which the researchers describe in a paper published today in Science, uses the same messenger ribonucleic acid (mRNA) technology employed in the Pfizer and Moderna SARS-CoV-2 vaccines. This mRNA technology that enabled those COVID-19 vaccines was pioneered at Penn. Tests in animal models showed that the vaccine dramatically reduced signs of illness and protected from death, even when the animals were exposed to flu strains different from those used in making the vaccine.

The strategy employed by the Penn Medicine researchers is to vaccinate using immunogens-a type of antigen that stimulates immune responses-from all known influenza subtypes in order to elicit broad protection. The vaccine is not expected to provide "sterilizing" immunity that completely prevents viral infections. Instead, the new study shows that the vaccine elicits a memory immune response that can be quickly recalled and adapted to new pandemic viral strains, significantly reducing severe illness and death from infections.

The experimental vaccine, when injected and taken up by the cells of recipients, starts producing copies of a key flu virus protein, the hemagglutinin protein, for all twenty influenza hemagglutinin subtypes-H1 through H18 for influenza A viruses, and two more for influenza B viruses.

Reference:

Arevalo, C. P., Bolton, M. J., Le Sage, V., Ye, N., Furey, C., Muramatsu, H., Alameh, M. G., Pardi, N., Drapeau, E. M., Parkhouse, K., Garretson, T., Morris, J. S., Moncla, L. H., Tam, Y. K., Fan, S. H. Y., Lakdawala, S. S., Weissman, D., & Hensley, S. E. (2022b). A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science, 378(6622), 899–904. DOI: 10.1126/science.abm0271