A Multivalent mRNA Influenza Vaccine for Broad Immunity to Seasonal and Pandemic Influenza in Animal Models

Influenza vaccines are given each year to protect against specific strains circulating in humans likely to be the most prevalent during flu season. These vaccines are a critical public health tool to fight seasonal influenza but are unlikely to provide protection against viruses emerging from animals with the potential to cause pandemics. Researchers funded by the National Institute of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Response (CEIRR) and Collaborative Influenza Vaccine Innovation Centers (CIVICs) developed an experimental multivalent influenza vaccine that extends immune responses beyond the narrow protection afforded by seasonal vaccines. 

The study led by Dr. Scott Hensley’s lab and in collaboration with Dr. Drew Weissman’s lab, at the University of Pennsylvania, and part of the Duke CIVIC Vaccine Center (DCVC), assessed the effectiveness of an mRNA vaccine targeting the viral surface glycoprotein hemagglutinin. The authors apply recent advances in mRNA technology used in current COVID-19 vaccines to deliver more antigens at once than what is feasible with other approaches. 

Graphical depiction of 20 HA mRNA-lipid nanoparticle vaccine. Image credit: NIH Director's Blog
Graphical depiction of 20 HA mRNA-lipid nanoparticle vaccine. Image credit: NIH Director's Blog

Twenty unique mRNAs encoding hemagglutinins from the 18 known influenza A subtypes and two influenza B lineages were administered to mice and ferrets using a single lipid nanoparticle vaccine system. The multivalent mRNA vaccine was highly effective at stimulating cross-reactive and subtype-specific antibodies in both mice and ferrets and protected animals from severe illness following infection with strains both like and unlike those used to make the vaccine. 

By incorporating 20 diverse antigens into a single vaccine, investigators demonstrate a many-in-one approach that elicits broad protection. This work advances development of a “universal” influenza vaccine to defend against seasonal and pandemic flu. To read more about this study, check out the NIH Director’s Blog and Penn Medicine News. To read the full article, click here.

Arevalo, CP et al. (2022) A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science. 378: 899-904.