Fig. 1: Antigenic mismatch of the H3N2 component of the 2019–2020 Northern Hemisphere influenza vaccine.

a Crystal structure of the HA trimer of A/Victoria/361/2011 (PDB accession code 4O5I) with the amino acid substitutions that differ between egg-adapted and wild-type A/Kansas/14/2017 (positions 186, 190, and 219) shown in black and the amino acid substitutions that differ between wild-type A/Kansas/14/2017 and other 3c2.A H3N2 subclades in antigenic sites A (positions 128, 138, 142, and 144) and B (positions 159, 160, and 193) shown in blue and red, respectively. The receptor-binding pocket is indicated in yellow. b Neutralizing antibody titers (FRNT₉₀) to wild-type A/Kansas/14/2017 (3c3.A) and egg-adapted A/Kansas/14/2017 (3c3.A-egg) using wild-type A/Kansas/14/2017 antisera (n = 3 ferrets, each data point represents the geometric mean titer from three independent experiments). Data are presented as mean ± SEM. Log₂-transformed antibody titers were compared using RM one-way ANOVA corrected for multiple comparisons (Bonferroni method). P-values < 0.05 are indicated. c Neutralizing antibody titers (FRNT₉₀) to wild-type A/Kansas/14/2017 (3c3.A) and egg-adapted A/Kansas/14/2017 (3c3.A-egg) using egg-adapted A/Kansas/14/2017 antisera (n = 3 ferrets, each data point represents the geometric mean titer from three independent experiments). Data are presented as mean ± SEM. Log₂-transformed antibody titers were compared using RM one-way ANOVA corrected for multiple comparisons (Bonferroni method). P-values < 0.05 are indicated. d, e Neutralizing antibody titers (FRNT₉₀) to a panel of H3N2 viruses using wild-type A/Kansas/14/2017 and egg-adapted A/Kansas/14/2017 antisera (n = 3 ferrets per group, each data point represents the geometric mean titer from three independent experiments). 3c3.A virus with 3c2.A site A possesses amino acid substitutions A128T, S138A, G142R, and K144S. 3c3.A virus with 3c2.A site B possesses amino acid substitutions S159Y, K160T, and S193F. 3c2.A virus with 3c3.A site A possesses amino acid substitutions T128A, A138S, R142G, and S144K. 3c2.A virus with 3c3.A site B possesses amino acid substitutions Y159S, T160K, and F193S. Data are presented as mean ± SEM. Log₂-transformed antibody titers were compared using RM one-way ANOVA corrected for multiple comparisons (Bonferroni method). Significant differences relative to 3c3.A are indicated (p < 0.05). Source data are provided as a Source Data file.