Intrahost HA polymorphisms and culture adaptation shape antigenic profiles of H3N2 influenza (2017-2018) season

Accurate antigenic characterization of influenza viruses is critical for vaccine strain selection but is often confounded by intrahost genetic diversity and culture-induced adaptations. We analyzed H3N2 influenza A positive nasopharyngeal specimens collected during the 2017 to 2018 influenza season to determine how virus propagation in MDCK cells affects viral genetic and antigenic properties. By combining deep sequencing with serological analysis of clinical specimens and cultured isolates, we demonstrate that virus propagation in MDCK cells imposes strong purifying selection and alters antigenic profiles. Furthermore, we show that minor amino acid polymorphisms present in clinical samples can generate measurable antigenic diversity, emphasizing that natural intrahost variation shapes antigenic outcomes.