Antigenic assessment of the H3N2 component of the 2019-2020 Northern Hemisphere influenza vaccine

Abstract

The 2019-2020 Northern Hemisphere influenza vaccine includes antigens from 3c3.A H3N2 viruses; however, over half of circulating H3N2 viruses belong to subclade 3c2.A1b. Here, we analyze antibody responses elicited by the egg-adapted 3c3.A H3N2 vaccine strain in ferrets and humans. We find that this vaccine strain elicits antibodies that have reduced reactivity to a wild-type 3c3.A strain and very limited reactivity to 3c2.A strains, including the currently circulating 3c2.A1b strain.

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.

Fig. 2. Neutralizing antibody titers (FRNT₉₀) to a panel of H3N2 viruses in sera from adults (n = 62) who received the 2019–2020 Northern Hemisphere influenza vaccine.

a Pre- and post-vaccination titers. Each data point represents the geometric mean titer from two independent experiments. Thick horizontal lines show the geometric means and error bars indicate the 95% confidence intervals. Log₂-transformed antibody titers were compared using RM one-way ANOVA corrected for multiple comparisons (Bonferroni method). P-values < 0.05 are indicated. b Fold change of geometric mean neutralizing antibody titers (FRNT₉₀) upon vaccination. Post-vaccination titers were divided by pre-vaccination titers to calculate fold change. Thick horizontal lines show the geometric means and error bars indicate the 95% confidence intervals. Log₂-transformed antibody titers were compared using RM one-way ANOVA corrected for multiple comparisons (Bonferroni method). P-values < 0.05 are indicated. c Seroconversion rates upon vaccination. Light gray bars indicate at least a twofold increase in antibody titer. Dark gray bars indicate at least a fourfold increase in antibody titer. 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. Source data are provided as a Source Data file.