Influenza (flu) is a respiratory illness affecting about 8% of Americans a year and, along with pneumonia, is among the top ten leading causes of death in the US. The elderly and young are particularly vulnerable to complications from the flu, which can range in severity from ear infections to multiple organ failure. To reduce the number and severity of flu illnesses, vaccines are designed every year to match the flu strains most likely to circulate, with varying success in how precise the match is. A poor match can reduce the amount of protection provided by flu vaccination, leaving many vulnerable to potentially severe infection outcomes.
To develop flu vaccines, scientists take advantage of the flu virus’ ability to bind to red blood cells. Typically, scientists use a test, called the hemagglutination inhibition assay (HI test), to see if a vaccine candidate impedes the binding between a flu strain and red blood cells. However, the current leading strain of flu, influenza A/H3N2, has characteristics that render the HI test ineffective. Specifically, the A/H3N2 flu viruses may have genetic changes that prevents them from binding to sugar molecules called glycans on the surface of red blood cells.
A major goal of the Common Fund’s Glycoscience Program is to develop tools that make the analysis of glycans, like those found on red blood cells, accessible to the research community. In research supported by the Glycoscience Program, Dr. Geert-Jan Boons and colleagues used a novel glycan microarray (a technology that allows for the analysis of a large number of glycans at once) to determine what kind of glycans are required for the A/H3N2 flu strain to bind red blood cells. They then engineered the absent glycans and installed them on chicken and turkey blood cells, which are commonly used in tests of red blood cells’ ability to bind. The addition of the engineered glycans enabled the A/H3N2 flu strain to be responsive to the HI test. Using this technology, the researchers found evidence of subpar matches between the circulating flu strains and some flu vaccines. This work has the potential to influence the design of better flu vaccines in the future.
Reference
- Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses. F. Broszeit, R.J. van Beek, L. Unione, T.M. Bestebroer, D. Chapla, J.-Y. Yang, K.W. Moremen, S. Herfst, R.A.M. Fouchier, R.P. de Vries, and G.-J. Boons. Nature Communications. 2021 Sep 14; 12(1):5449.
