Brief analysis of spike mutations in XEC SARS-CoV-2 variant

Analysis by Jesse Bloom on Oct-16-2024

TLDR: XEC has modest antigenic change relative to KP.2 (current USA-recommended vaccine) and more mild change relative to KP.3.1.1 (current dominant variant), but is not a big antigenic jump

Note: this analysis only looks at spike amino-acid mutations, not mutations elsewhere in genome

Growth estimates from Trevor Bedford lab: https://nextstrain.github.io/forecasts-ncov/

XEC likely has the highest growth rate of any current SARS-CoV-2 variant, including the currently dominant KP.3.1.1

Plot of mutations generated using https://github.com/jbloom/SARS2-clade-spike-diffs

All currently relevant strains have many mutations relative to ancestral Wuhan strain

(>50 amino-acid substitutions, at least 8 deleted residues, and in some cases an insertion)

Not shown in above plot: all variants also have an insertion of MPLF at site 16

Plot of mutations generated using https://github.com/jbloom/SARS2-clade-spike-diffs

However, all currently relevant strains are fairly close to each other and the vaccine booster

This plot just shows sites in spike that differ among the plotted variants.

(recommended vaccine booster in USA)

(parent of all variants in spike)

XEC has only a few spike mutations relative to KP.3.1.1, and only a modest number relative USA-recommended vaccine booster KP.2

• Q493E (also in KP.3.1.1 but not KP.2): increases ACE2 affinity, some antibody escape
• lacks R346T (KP.2 has this mutation, but KP.3.1.1 does not): this is a site of moderate antigenic importance
• T22N (not in KP.3.1.1 or KP.2): may cause modest antibody escape including by putting RBD more down
• F59S (not in KP.3.1.1 or KP.2): may cause some antibody escape including by putting RBD more down
• lacks S31del (deletion in KP.3.1.1 but not KP.2): this mutation may cause modest escape and put RBD more down, could be somewhat redundant with T22N

Summary:

XEC may be modestly more fit than KP.3.1.1

However, it does not represent a dramatic antigenic jump from either KP.3.1.1 or KP.2 (eg, it is more gradual evolution, not a big jump). It therefore represents continual incremental evolution that may involve a modest antigenic advantage.