Why Is H3N2 Flu Vaccine Effectiveness Reduced?

The effectiveness of the annual influenza vaccine has declined in recent years, especially for the H3N2 component.

Australian flu vaccines for 2017 have proven to be only 33 percent effective against H3N2 viruses.

A major cause for this lack in effectiveness has been attributed to the egg-based vaccine production process.

The subtype of influenza in this study, H3N2, is one of several subtypes shown to mutate when grown in chicken eggs, and these researchers say the new findings further support the case for alternative approaches to growing the virus.

It is common to use chicken eggs for culturing clinical isolates and for large-scale production of flu vaccines.

However, influenza viruses often mutates to adapt to being grown in chicken eggs, which can influence antigenicity and hence impact vaccine effectiveness.

“Now we can explain at an atomic level why egg-based vaccine production is causing problems,” said Nicholas Wu, Ph.D., first author of this study. 

The subtype of influenza in this study, called H3N2, is one of several subtypes shown to mutate when grown in chicken eggs.

“Any influenza viruses produced in eggs have to adapt to growing in that environment and hence generate mutations to grow better,” explained study senior author Ian Wilson, D.Phil., Hansen Professor of Structural Biology at The Scripps Research Institute.

The new study shows exactly why egg-based manufacturing is a problem for the H3N2 subtype. When grown in eggs, the H3N2 subtype mutates a key protein to better attach to receptors in bird cells.

Specifically, there was a mutation called L194P on the virus’s hemagglutinin glycoprotein. This mutation disrupts the region on the protein that is commonly recognized by our immune system.

This means a vaccine containing the mutated version of the protein will not be able to trigger an effective immune response.

This leaves the body without protection against circulating strains of H3N2.

In fact, Wu’s analysis shows that the current strain of H3N2 used in vaccines already contains this specific mutation L194P on the hemagglutinin glycoprotein.

The researchers say further studies are needed to investigate replacing the egg-based system.

This study was supported by National Institutes of Health R56 AI117675 and R56 AI127371. JCP was supported by National Institutes of Health R01 AI114730. SEH was supported by National Institutes of Health R01 AI113047 and R01 AI108686. NCW was supported by a Croucher Foundation Fellowship.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors declared no competing interests.