Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants

Figures

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  Figure 1.. Mutations and frequencies of JN.1 subvariants dominant in Spring 2025 (A) Spike mutations present in selected JN.1 subvariants. (B) Structural diagram of SARS-CoV-2 spike protein. Spike mutations present in KP.3.1.1 are highlighted in cyan. Spike mutations present in the other JN.1 subvariants studied herein are highlighted in red. (C) Relative frequencies of SARS-CoV-2 variants from 02/01/2025 to 08/01/2025 in the indicated regions. Numbers of sequences analyzed in parentheses above each subpanel. Data from GISAID.

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  Figure 2.. Serum antibody evasion of recent JN.1 subvariants (A and B) Serum neutralizing titers (ID50) against VSV-based pseudoviruses bearing spike proteins of JN.1, KP.2, KP.3, KP.3.1.1, XEC, LP.8.1, LP.8.1.1, LP.8.1.9, MC.10.1, LF.7, or LF.7.2.1 for samples from 20 recipients of KP.2 MV boosters at ~1-month post-booster (A) (“KP.2 MV”) and 20 US-based adults who chose not to receive a KP.2 MV booster (B) (“No KP.2 MV”). The geometric mean ID50 titer (GMT) is presented at the top. The fold change in GMT for each virus compared to XEC is also shown immediately above the symbols. Statistical analyses used Wilcoxon matched-pairs signed-rank tests, compared to XEC. n, sample size; ns, not significant. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Numbers under the dotted lines denote numbers of serum samples that were under the limit of detection (ID50 < 50). (C) Antigenic map generated using all neutralization data from (A) and (B). One antigenic unit (AU) represents an approximately 2-fold change in ID50 titer. Serum samples and viruses are shown as squares and dots, respectively. (D and E) Serum neutralizing titers (ID50) against VSV-based pseudoviruses bearing spike proteins of…

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  Figure 3.. Monoclonal antibody evasion of recent JN.1 subvariants (A) Pseudovirus neutralization IC50 values for mAbs against the indicated JN.1 subvariants. (B) Modeling of the effects of spike H445R mutation on interaction with CYFN1006–1. (C) Modeling of the effects of spike A475V, in the presence of other spike mutations, on interactions with 19–77. (D) Modeling of the effects of spike A435S on the spike 371–376 loop. Mutations modeled using the mutagenesis function in PyMOL (see STAR Methods).

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  Figure 4.. ACE2 binding of recent JN.1 subvariants (A) Sensitivity of 11 JN.1 subvariants to hACE2 inhibition. IC50 values are noted, as are fold differences in IC50 relative to XEC. (B) Modeling of the effects of spike A475V on interactions with spike residue N487, which normally forms hydrogen bonds with hACE2. Electrostatic potential of hACE2 indicated by surface color, according to the scale at bottom, in KT/e. (C) Sensitivity of 4 recent JN.1 subvariants to hACE2 inhibition. Data are shown as mean ± standard error of mean (SEM) for three technical replicates. Fold changes of variants that emerged later than the reference strain in (A) and (C) are colored in green to indicate greater affinity to ACE2 than the reference strain or in red to indicate lower affinity to ACE2.