Emergence of neutralizing RBD antibodies following Omicron infection with limited activity against ancestral SARS-CoV-2

Convergent IGHV3-53/3-66 antibodies elicited by Omicron BA.1 infection broadly neutralize emerging SARS-CoV-2 variants

Structural and mutational analyses define distinct molecular routes to broad SARS-CoV-2 receptor-binding domain recognition

Two human-derived monoclonal antibodies are characterized that recognize conserved epitopes on the SARS-CoV-2 RBD and retain activity across antigenically distinct variants, and conserved, mutationally constrained epitopes may serve as targets for vaccines designed to elicit antibody responses resilient to ongoing SARS-CoV-2 evolution and future sarbecovirus emergence.

Allosteric effects of CDR-H3 mutations modulate binding and neutralization of a conserved SARS-CoV-2 RBD-targeting antibody

Comparing wild-type XG83 and modified MuXG83 shows how allosteric tuning affects antibody-antigen compatibility in developing variations like Omicron, and indicates that non-epitope (potentially allosteric) changes to CDRH3 are also important while investigating potential development and neutralization before advancement.

Serum Escape Landscape of SARS-CoV-2 Omicron JN.1 and XEC RBD Under COVID-19 Vaccine Breakthrough Immunity in China

Population immune pressure from vaccination and prior infection continues to drive the evolution of SARS-CoV-2. Systematic characterization of RBD mutations under complex immune backgrounds is essential for understanding viral adaptation and evolutionary trajectories. Here, we applied a deep mutational scanning (DMS) to comprehensively map the neutralization escape landscape of the Omicron variant JN.1 and its descendant lineage XEC, under immune pressure from individuals who experienced Omicron breakthrough infections following three doses of inactivated vaccines. A neutralization escape map for the single amino acid substitutions in the RBD of JN.1 or XEC was generated, and the escape efficiency of each mutation was determined. The results show that RBD escape mutations are hierarchically organized: low-intensity signals are widespread, whereas high-intensity escape is confined to a few key sites. These escape mutations are not confined solely to the receptor-binding motif (RBM) but are broadly distributed across the entire RBD. Many escape sites could accommodate multiple amino acid substitutions. Integration of DMS data with genomic surveillance of circulating variants from 2024 to 2025 revealed significant overlap between experimentally identified escape sites and mutations observed in natural isolates. This overlap increased substantially in 2025, with site concordance rising from 27.17% and 26.81% to 45.09% and 47.10% for JN.1 and XEC, respectively. The natural prevalence of these escape mutations is further shaped by factors such as receptor-binding affinity, protein stability, and epistatic interactions. Overall, our findings suggest that SARS-CoV-2 antigenic evolution follows the pattern of multiple pathways within a constrained space, providing new insights into the adaptive mechanisms of Omicron-derived variants under hybrid immune pressure.

Antibody evasion and receptor binding of SARS-CoV-2 variants PQ.16.1.1 and RK.1

Evaluations utilizing surface plasmon resonance and pseudovirus assays demonstrate that these sublineages exhibit significantly reduced human ACE2 receptor engagement compared to their parental strain, which suggests these variants will soon spread globally and emphasize the critical need for ongoing surveillance to monitor D420N-carrying lineages.

Structural and functional dissection of neutralisation differences among SARS-CoV-2 variants using antigenicity prediction and CR3022 binding analysis

A combined experimental and computational characterization of SARS-CoV-2 variant-specific neutralisation across infection, vaccination and hybrid immunity-driven cohorts is provided, offering a hypothesis-generating framework to contextualize observed differences in antibody responses and epitope recognition across variants.