Comparison of the neuraminidase antigenicity in recently circulating influenza A and vaccine viruses

ABSTRACT Neuraminidase (NA or N) antigens in circulating influenza viruses are not extensively evaluated for vaccine strain selection like hemagglutinin (HA or H) even though viral-based influenza vaccines include the recommended strain NA in varying amounts. As NA can also elicit a protective response, we assessed the antigenic similarity of the NAs from human H1N1 and H3N2 viruses that were prevalent between September 2019 to December 2020 to NAs from several recently recommended vaccine strains. To eliminate the dependence on isolates, the enzyme-linked lectin assay for analyzing NA antigenicity was performed with reverse genetic viruses carrying the same HA. Our results show that ferret antisera against NAs from the recommended H1N1 and H3N2 vaccine strains for the 2020-21 northern hemisphere influenza season recognize and inhibit the most prevalent circulating N1s and N2s, suggesting the NAs from the influenza A vaccine and circulating strains are antigenically similar. Comparisons of the recent N2s also revealed a bias in the reactivity of NA antisera from the egg and cell-based H3N2 vaccine strains due to a C-terminal substitution, indicating the C-terminus can influence N2 antigenicity and should receive consideration during the H3N2 strain selection.