Computationally Optimized H1 and H3 Hemagglutinin Messenger RNA Vaccines Confer Broad Protective Immunity Against Modern Influenza Viruses
The hemagglutinin (HA) glycoprotein of seasonal influenza viruses undergoes continual antigenic drift, contributing to vaccine mismatch and reduced effectiveness of strain-specific seasonal vaccines. Although vaccination remains the most effective strategy for preventing influenza disease, conventional egg-based vaccine production requires several months and may not keep pace with viral…
Seasonal influenza vaccines often fall short due to antigenic drift in the hemagglutinin (HA) glycoprotein, rendering strain-specific vaccines less effective. Conventional egg-based production of these vaccines can take several months, falling behind viral evolution. Messenger RNA (mRNA) vaccines present a faster alternative, allowing rapid updates to encode emerging antigens through a scalable, cell-free manufacturing process.
Researchers harnessed mRNA technology with Computationally Optimized Broadly Reactive Antigens (COBRA) to create broadly protective influenza HA vaccines targeting H1 and H3 strains. These COBRA H1 and H3 mRNA vaccines prompted strong antibody responses—antigen-specific IgG, hemagglutination inhibition (HAI), and neutralizing antibodies—in both naïve and pre-immune mice against diverse historical and contemporary influenza strains.
Furthermore, vaccination boosted cellular immunity, evidenced by expanded antigen-specific antibody and cytokine-secreting cells. This effect was amplified in animals already immune to influenza, with increased frequency of IFN-γ producing cells recognizing conserved HA stalk-based peptides. The study concludes that COBRA HA encoding mRNA vaccines can harness immunological memory while broadening responses to conserved HA epitopes, offering a promising strategy for next-generation influenza vaccination.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
