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In vivo evolution of antibody CR3022 expands cross-neutralization of SARS-CoV-2 variants and informs pan-sarbecovirus immunity

Fu et al. use Ig-humanized mice expressing the germline CR3022 heavy chain to reveal how somatic hypermutation rapidly adapts this antibody class for broad sarbecovirus recognition. Sequential immunization drives CR3022-like maturation, while structural analyses show that increased affinity and breadth arise from subtle polar and electrostatic refinements.

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