Low effectiveness of the H3N2 vaccine could be due to manufacturing process

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The effectiveness of the seasonal influenza vaccine, particularly for H3N2, has declined in recent years. A new study has reported that the common practice of growing influenza vaccine components in chicken eggs disrupts the major antibody target site on the virus surface, which leads to the vaccine being less effective in humans.

The manufacturing process of the vaccine involves injecting the influenza into chicken eggs to allow viral replication to occur. The fluid is then purified from the eggs in order to retrieve the virus for vaccines.

Ian Wilson (The Scripps Research Institute, CA, USA), a senior author of the study published in PLoS Pathogens, explained: “Any influenza viruses produced in eggs have to adapt to growing in that environment and hence generate mutations to grow better.” In particular, H3N2 is one of several influenzas known to mutate when grown in chicken eggs.

Researchers used x-ray crystallography to demonstrate that when H3N2 is grown in eggs, a key protein mutates to better attach to receptors in bird cells. Specifically, the L194P mutation on the virus’s hemagglutinin glycoprotein (HA) disrupted the region on the protein that is commonly recognized by our immune system – rendering the flu vaccine to be less effective in humans if it contains this mutatation.

As the H3N2 influenza is becoming more prevalent, this study reveals why egg-based manufacturing is a problem. According to Nicholas Wu (The Scripps Research Institute), current H3N2 strains used in vaccines appear to contain the L194P mutation on HA: “Vaccine producers need to look at this mutation,” he cautioned.

To conclude, the researchers commented in their study that: “As annual vaccination remains the major preventive measure against influenza virus, it may be beneficial to accelerate the consideration of alternative approaches for influenza vaccine production to optimize the protective effectiveness of the vaccine.”

Wilson added: “Other methods are now being used and explored for production of vaccines in mammalian cells using cell-based methods and recombinant HA protein vaccines.”

Sources: Wu NC, Zost SJ, Thompson AJ et al. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS Pathog. 13(10), e1006682 (2017); www.scripps.edu/news/press/2017/20171030wilson.html

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