Sequencing analysis of B cell receptor repertoire in a BNT162b2 vaccinee after SARS-CoV-2 Omicron BA5 breakthrough infection: a case study 4586

Description Background The magnitude of mRNA vaccine-induced memory B cell responses recalled by SARS-CoV-2 breakthrough infection remains incompletely investigated. Methods We conducted B cell receptor (BCR) repertoire sequencing and used a deep learning model to understand recalled BCR quantitively in a BNT162b2 vaccinee, who generated ultrapotent class-I broadly neutralizing antibodies (bnAbs) after Omicron BA.5 breakthrough infection. Results We obtained 3308 paired BCR sequences including 44.4% to receptor binding domain and 3.07% to N-terminal domain compared with CoV-AbDab. The dominant IGHV clonotype with a frequency of over 10% was IGHV3-23 followed by IGHV3-33 and IGHV4-59, from which no ultrapotent bnAbs were generated. Instead, the minor IGHV clonotype IGHV3-66 with a frequency of less than 2.5% gave rise to ultrapotent receptor binding domain (RBD)-specific class-I bnAbs, which neutralized all Omicron subvariants tested with IC50 values less than 10 ng/mL. Clearly, these ultrapotent bnAbs were not derived from the IGHV1-58 class-I bnAb ZCB11, which was previously found in the same BNT162b2-vaccinee before the breakthrough infection. Conclusion This study indicated that breakthrough infection can recall ultrapotent class-I bnAbs from BNT162b2-induced memory B cells displaying distinct and minor clonotypes.