SJ-20-0031 – HA Modifications for Improved Influenza Vaccine Production

  • increased viral replication while maintaining viral fitness and virulence
  • more robust immunological response due to hyperactivation of key interferon and inflammatory pathways
  • result in higher production yields as well as a stronger immunological response

Abstract

Currently, most influenza vaccine virus strains are produced using embryonated chicken eggs; however, this method often introduces mutations into the viral genome that can reduce overall vaccine effectiveness. While producing vaccine virus strains using human cell lines is more desirable, it is more expensive due to lower yields in comparison to chicken eggs. The recent expiration of the reverse genetics patent for influenza opens new opportunities to directly modify viral genes used for vaccine production to increase yield and lower production cost. Researchers at St. Jude have discovered two highly conserved nucleic acid sites within the hemagglutinin (HA) gene of the H1N1 influenza virus that allows the virus to replicate at a much higher rate in a shorter amount of time. These specific sites are associated with adenosine methylation (called m6A), and when mutated, result in increased viral replication while maintaining viral fitness and virulence. This increased replication rate also results in a more robust immunological response due to hyperactivation of key interferon and inflammatory pathways. Ultimately, incorporation of these two mutations into vaccine virus strains may ultimately result in higher production yields as well as a stronger immunological response to the antigen when compared to standard dosage. International Application Published as WO 2022/051327 More information is available under a confidentiality agreement, we are seeking partners to produce vaccine using these methods.

Advantages

Researchers at St. Jude have discovered two highly conserved nucleic acid sites within the hemagglutinin (HA) gene of the H1N1 influenza virus that allows the virus to replicate at a much higher rate in a shorter amount of time. These specific sites are associated with adenosine methylation (called m6A), and when mutated, result in increased viral replication while maintaining viral fitness and virulence. This increased replication rate also results in a more robust immunological response due to hyperactivation of key interferon and inflammatory pathways. Ultimately, incorporation of these two mutations into vaccine virus strains may ultimately result in higher production yields as well as a stronger immunological response to the antigen when compared to standard dosage.

Potential Applications

Currently, most influenza vaccine virus strains are produced using embryonated chicken eggs; however, this method often introduces mutations into the viral genome that can reduce overall vaccine effectiveness. While producing vaccine virus strains using human cell lines is more desirable, it is more expensive due to lower yields in comparison to chicken eggs. The recent expiration of the reverse genetics patent for influenza opens new opportunities to directly modify viral genes used for vaccine production to increase yield and lower production cost.

Contact Information

Name: Scott Elmer

Email: scott.elmer@stjude.org

Phone: 901-595-2756