TABLE. Predominant amino acid deletions and substitutions in the receptor binding domain (residues 332–527) and residue 31 of the spike protein relative to XBB.1.5* among Omicron lineage groups with ≥5% prevalence† — United States, May 14, 2023–September 14, 2024.
| Lineage | Spike protein amino acid substitutions |
|||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 31§,¶ | 332 | 346§,** | 356 | 368 | 403 | 445** | 450** | 452§,** | 455§,** | 456§,** | 475** | 478 | 481 | 483 | 484** | 486§,** | 490** | 493** | 521 | |
| Reference sequence: XBB.1.5* |
S |
I |
T
|
K |
I
|
R |
P
|
N |
L |
L |
F |
A |
K
|
N |
V |
A
|
P
|
S
|
Q |
P |
| XBB |
—†† |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
S |
— |
— |
— |
| XBB.1.16-like (HF.1, XBB.1.16, XBB.1.16.1, and XBB.1.16.17) |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
R |
— |
— |
— |
— |
— |
— |
— |
| XBB.2.3 |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
S |
| EG.5-like (EG.5, EG.6.1, FD.1.1, FE.1.1, XBB.1.5.10, XBB.1.5.59, and XBB.1.5.72) |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
L |
— |
— |
— |
— |
— |
— |
— |
— |
— |
| FL.1.5.1-like (FL.1.5.1 and XBB.1.16.6) |
— |
— |
— |
— |
— |
— |
— |
— |
— |
— |
L |
— |
R |
— |
— |
— |
— |
— |
— |
— |
| HV.1 |
— |
— |
— |
— |
— |
— |
— |
— |
R |
— |
L |
— |
— |
— |
— |
— |
— |
— |
— |
— |
| HK.3-like (EG.5.1.8, GK.1.1, HK.3, JG.3, and XBB.1.5.70) |
— |
— |
— |
— |
— |
— |
— |
— |
— |
F |
L |
— |
— |
— |
— |
— |
— |
— |
— |
— |
| JD.1.1 |
— |
— |
— |
— |
— |
— |
— |
— |
— |
F |
L |
V |
— |
— |
— |
— |
— |
— |
— |
— |
| JN.1-like (JN.1, JN.1.13, JN.1.32, JN.1.7, JN.1.8.1, JN.1.4.3, KV.2, and XDP) |
— |
V |
R |
T |
L |
K |
H |
D |
W |
S |
— |
— |
— |
K |
— |
K |
— |
F |
— |
— |
| JN.1.16-like (JN.1.11.1, JN.1.16, KW.1.1, KP.1.2, and XDV.1) |
— |
V |
R |
T |
L |
K |
H |
D |
W |
S |
L |
— |
— |
K |
— |
K |
— |
F |
— |
— |
| KQ.1-like (JN.1.13.1, JN.1.18, and KQ.1) |
— |
V |
— |
T |
L |
K |
H |
D |
W |
S |
— |
— |
— |
K |
— |
K |
— |
F |
— |
— |
| KP.2-like (JN.1.16.1, KP.1.1, KP.2, KS.1, KP.4.1, and LF.3.1) |
— |
V |
— |
T |
L |
K |
H |
D |
W |
S |
L |
— |
— |
K |
— |
K |
— |
F |
— |
— |
| KP.3 (XEC§§) |
— |
V |
R |
T |
L |
K |
H |
D |
W |
S |
L |
— |
— |
K |
— |
K |
— |
F |
E |
— |
| LB.1-like (KP.1.1.3, KP.2.3, LB.1, and LP.1) |
Δ |
V |
— |
T |
L |
K |
H |
D |
W |
S |
L |
— |
— |
K |
— |
K |
— |
F |
— |
— |
| KP.3.1.1-like (MC.1) | Δ | V | R | T | L | K | H | D | W | S | L | — | — | K | — | K | — | F | E | — |
Abbreviations: A = alanine; C = cysteine; D = aspartic acid; Δ = deletion; E = glutamic acid; F = phenylalanine; G = glycine; H = histidine; I = isoleucine; K = lysine; L = leucine; M = methionine; N = asparagine; P = proline; Q = glutamine; R = arginine; RBD = receptor binding domain; S = serine; T = threonine; V = valine; W = tryptophan; Y = tyrosine.
* The XBB.1.5 spike protein sequence was used as a reference because of its inclusion in 2023–2024 COVID-19 vaccines. Substitutions present relative to Wuhan-Hu-1 are underlined. XBB.1.5-like lineages also include FD.2, XBB.1.42.2, XBB.1.5, XBB.1.5.1, XBB.1.9.1, and XBB.1.9.2.
† Lineages with identical spike residue 31 and RBD (residues 332–527) amino acid sequences were grouped with a representative lineage and denoted as “representative lineage-like.” Lineage groups with ≥5% prevalence in at least one 2-week period and substitutions present in ≥50% of sequences belonging to a lineage were included. Lineages were ordered by date of first appearance on CDC’s COVID Data Tracker.
§ Indicates sites of independent substitutions in at least two different evolutionary lineages.
¶ Residue 31 in the N-terminal domain of the spike protein is included because of multiple independent acquisition of deletions in different descendant lineages of JN.1.
** Indicates sites identified in a previous study (https://www.nature.com/articles/s41586-021-04385-3) associated with in vitro reductions in binding by monoclonal antibodies that were previously Food and Drug Administration–authorized.
†† Dashes indicate the same amino acid as the reference sequence.
§§ XEC is a recombinant of JN.1 lineages KS.1.1 and KP.3.3 and contains the same RBD sequence as KP.3. XEC also has substitutions T22N and F59S.