8faw_antigenic

Antigenic regions of influenza H3 HA, with the glycans

HA from influenza A/Victoria/22/2020 (H3N2) bound to LSTc, an analogue of the alpha-2,6 sialylated receptor (PDB 8FAW). HA1 is colored by the classical antigenic region each site belongs to, taken from Table 2 of Stray & Pittman (2012), Virology Journal 9:91:

indigo — site A
cyan — site B
green — site C
purple — site D
teal — site E
light gray — HA1, not in a defined antigenic region
mid gray — HA2
black — the LSTc receptor analogue
yellow — host N-glycans

Every residue carries its site in HA1 or HA2 numbering — 145_HA1, 1_HA2 — shown on mouseover.

Antigenic regions of influenza H3 HA

indigo — site A
cyan — site B
green — site C
purple — site D
teal — site E
light gray — HA1, not in a defined antigenic region
mid gray — HA2
black — the LSTc receptor analogue

Glycans are hidden.

Every residue carries its site in HA1 or HA2 numbering — 145_HA1, 1_HA2 — shown on mouseover.

HA mutations between a 2009 and 2025 H3N2 strain

Structure of H3N2 HA (PDB 8FAW) with red indicating every site that differs between A/Perth/16/2009 (the H3N2 component of the 2010-2011 vaccine) and the subclade K strain A/Darwin/1415/2025 (the H3N2 component of the 2026-2027 vaccine). Sites that did not change shown in gray, and the sialic-acid receptor analogue is shown in black.

27 of the 43 ectodomain mutations are at sites in the classically defined antigenic regions: eight in site A, nine in site B, four in site C, two in site D, four in site E. All 27 are among the 40 at sites in the structure shown here.

The HA sequences for the two strains are GQ293081 and PX422923.

HA mutations between the 2025-2026 (J.2) and 2026-2027 (K) H3N2 vaccine strains

Structure of H3N2 HA (PDB 8FAW) with red indicating every site that differs between 2025-2026 vaccine strain (A/District Of Columbia/27/2023, subclade J.2) and the 2026-2027 vaccine strain (A/Darwin/1415/2025, subclade K). Sites that did not change shown in gray, and the sialic-acid receptor analogue is shown in black.

They differ at 10 sites:

Three mutations in antigenic region A: T135K, S144N, N145S
Three mutations in antigenic region B: N158D, I160K, K189R
One additional HA1 mutation outside the defined antigenic regions: Q173R
One HA2 mutation: S49N
Two mutations at sites not in the structure PDB 8FAW shown here: K2N and T328A

The HA sequences for the two strains are PV280355 and PX422923.

Subclade K with antigenic region D sites 222 and 223

Structure of H3N2 HA (PDB 8FAW) with red indicating every site that differs between 2025-2026 vaccine strain (A/District Of Columbia/27/2023, subclade J.2) and the 2026-2027 vaccine strain (A/Darwin/1415/2025, subclade K), and purple showing site 222 and 223 in antigenic region D.