Scientists Develop Method to Track Antigenic Drift in Influenza A(H3N2) Viruses

Influenza activity is on the decline in the United States overall, although recent activity is still elevated, and now investigators are beginning to look ahead to next season.

According to new preliminary 2018-2019 burden estimates from the US Centers for Disease Control and Prevention (CDC), there have been 31.2 million to 35.9 million flu illnesses in the US as of March 23, 2019, resulting in as many as 508,000 hospitalizations and 46,800 deaths. The latest weekly FluView report notes that although influenza A(H1N1)pdm09 viruses predominated from October to mid-February, the number of respiratory specimens positive for influenza A(H3N2) viruses have since surged and made up more than 68% of all influenza A respiratory specimens in week 12 of 2019. In the same week, influenza B made up only 5.4% of respiratory specimens positive for the virus.

In a new study recently published in the journal Scientific Reports, a research team led by CDC investigators describes a new method of antigenically characterizing H3N2 influenza viruses, which may help better track antigenic drift in circulating viruses. The method may prove vital to the Global Influenza Surveillance and Response System’s work tracking the evolution of the virus’ antigenic subtype and selecting candidate vaccine viruses for the H3N2 component of seasonal flu vaccines, potentially making the vaccines more effective.

As flu vaccine manufacturing takes 4 to 6 months, selecting vaccine virus components requires a great deal of forecasting based on global surveillance data. In the study, the investigators note the difficulties in this forecasting and how antigenic divergence can lead to a significant vaccine mismatch and reduced vaccine effectiveness. The new test reduces antigenic mischaracterization resulting from virus adaptation to cell culture, and may replace antigenic monitoring of circulating viruses often currently conducted using hemagglutination inhibition assay, which has not been effective with H3N2 viruses.

“In this study, we detail the antigenic characterization of influenza A(H3N2) viruses using a new assay, high-content imaging-based micro-neutralization test (HINT),” explain the authors, who used HINT and genomics to assess antigenic relatedness among H3N2 viruses circulating during 2011—2018 and confirm the role of particular amino acid substitutions in the hemagglutinin played in immune escape. “We also demonstrated that this assay can be used to directly characterize viruses in primary human specimens, highlighting the future potential of this assay to antigenically characterize authentic virus populations and without the need for virus propagation in cell culture. This new technique is a promising approach to expedite detection of antigenic drift variants among rapidly evolving influenza A(H3N2) viruses.”

The HINT assay offers a way for investigators to directly analyze patients’ respiratory samples rather than growing the virus in cell culture, which can introduce new mutations, and the CDC has called the new method an important scientific achievement for vaccine virus selection. “Notably, HINT proved to be useful for directly assessing the antigenic relatedness of A(H3N2) virus isolates and viruses in human respiratory specimens, which will increase throughput and directly characterizes the viruses produced in the human airway,” the investigators concluded. “Thus, HINT offers a valuable addition to the current laboratory tools available for analysis of antigenic relatedness.”