H3_prot_struct

Subclade K mutations (relative to 2025-2026 vaccine) also indicating sites 222 and 223

Structure of H3N2 HA (PDB 8FAW) with red indicating every site that differs between the 2025-2026 vaccine strain (A/District Of Columbia/27/2023, subclade J.2:S145N) and the 2026-2027 vaccine strain (A/Darwin/1415/2025, subclade K), and purple showing sites 222 and 223 in antigenic region D. A sialic-acid analog bound to the HA is shown in black sticks.

Subclade K and J.2:S145N differ at 10 sites (shown in red):

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 shown here: K2N and T328A

In addition, sites 222 and 223 are colored purple as they are sites of emerging mutations in subclade K that have a large antigenic effect.

Subclade K mutations (relative to 2025-2026 vaccine)

Structure of H3N2 HA (PDB 8FAW) with red indicating every site that differs between the 2025-2026 vaccine strain (A/District Of Columbia/27/2023, subclade J.2:S145N) and the 2026-2027 vaccine strain (A/Darwin/1415/2025, subclade K). A sialic-acid analog bound to the HA is shown in black sticks.

Subclade K and J.2:S145N 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 shown here: K2N and T328A

Classically defined antigenic regions of influenza H3 HA

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, 22 sites: 121-127, 129, 131-138, 140, 142-146
cyan — site B, 19 sites: 155-160, 186, 188-190, 192-194, 196-199, 246, 247
green — site C, 9 sites: 49, 50, 53, 54, 271, 273, 275, 276, 278
purple — site D, 20 sites: 167, 201-207, 214, 216-220, 222, 223, 225-227, 242
teal — site E, 12 sites: 62, 63, 75, 78-83, 91, 92, 94
light gray — HA1, not in a defined antigenic region
mid gray — HA2
black — the LSTc receptor analogue

Sites are numbered in HA1 numbering, and all 82 of them are modeled in 8FAW. The regions are disjoint, so every colored site belongs to exactly one of them.

Glycans are hidden.