Method for improving seasonal flu vaccines also aids pandemic prediction

April 3, 2023
Scientists at St. Jude Children’s Research Hospital found mutations that can improve or impair flu vaccines and may give clues to assess the pandemic potential of flu viruses in nature.

Improving the seasonal influenza vaccine and public health specialists’ ability to predict pandemic potential in new flu strains may be possible due to new findings from scientists at St. Jude Children’s Research Hospital. The key is the stability of a viral protein that gains entry into human cells. The findings were published today in Science Advances.

“We found that the protein flu viruses use to enter cells, hemagglutinin, needs to be relatively stable and resistant to acid in an effective H3N2 flu vaccine,” said senior and co-corresponding author Charles Russell, Ph.D., St. Jude Department of Infectious Diseases. “We found a mutation in hemagglutinin that makes the virus grow better in eggs also causes a mismatch in the vaccine. The mutation makes the virus unstable and makes it look less human-like.”

While egg-adaptive mutations are a well-known weakness in many current flu vaccine pipelines, scientists currently do not consider viral protein stability when assessing flu strains to include in the annual vaccine. This study suggests that testing flu strains’ hemagglutinin for an antigenic match to circulating viruses, then including only those with higher stability, may improve the vaccine by preventing the incorporation of strains with unstable proteins.

The scientists also found that hemagglutinin stability could be measured to better predict the pandemic potential of novel flu strains. Flu viruses with the unstable protein could not transmit in the air between ferrets, a model used to infer likely properties in humans. Moreover, viruses with the more stable protein version had a high airborne transmission rate.

The study’s results suggest that by incorporating a simple experiment testing hemagglutinin stability, scientists may be able to better assess the pandemic potential risk of novel influenza viruses.

St. Jude Children’s Research Hospital release