Extended Data Fig. 9: B cells edited to express SARS-CoV-2 neutralizing antibodies.

a, Table lists amino-acid receptor-binding domain (RBD) differences from ancestral SARS-CoV-2. Residue numbers, based on the ancestral S protein, are indicated. b, Representative plots of edited cells expressing ZCB11 or S309 used to generate Fig. 7a. Cells were analyzed by flow cytometry using the S-protein RBD of the indicated SARS-CoV-2 variants conjugated to APC. Control cells were electroporated with the same RNP complex without HDRT (no HDRT). Numbers indicate the percentage of RBD-positive cells. c, Figure represents the mRNA-expressed antigen used to drive affinity maturation of the SARS-CoV-2 neutralizing antibodies ZCB11 and S309. As indicated, RBD antigens of the BA.5 (ZCB11) and XBB.1.5 (S309) Omicron variants were modified to include four additional glycans (white, pre-existing glycans; green, engineered glycans) that promote expression and immunogenicity⁴³. These RBDs were fused to the S-protein transmembrane domain through an 8-amino acid linker (GGGSGGTG). Numbers indicate S-protein position. d. A schedule of immunization and blood collection used to generate plasma and cells analyzed in Fig. 7 and panel (e). e, Neutralization studies of plasma against the BA.5 (ZCB11; n = 3 mice) or XBB.1.5 (S309; n = 5 mice) immunogen variants are presented. Panels characterize plasma before and after each of two vaccinations from mice engrafted with B cells edited to express the indicated antibody, summarized in Fig. 7b. Negative control (grey) indicates identically vaccinated mice without adoptive transfer. Black represents pooled sera from mice pre-immunization. Each curve is fitted to the mean of two independent replicates.