Discovery of a Novel Public Antibody Lineage Correlated With Inactivated SARS-CoV-2 Vaccine and the Resultant Neutralization Activity.

While the SARS-CoV-2 vaccine offers 70%-95% protection effectiveness against Coronavirus disease 2019 (COVID-19), a portion of recipients do not produce adequate protective immune responses, particularly, neutralizing antibodies (nAbs). Previous studies of COVID-19 patients have identified several public antibody lineages, such as IGHV3-30, IGHV3-33, IGHV3-53, IGHV1-58, and IGHV1-24. However, it remains unclear how these public antibodies evolve during vaccination or whether there are any special antibody lineages correlated with SARS-CoV-2 vaccination. In this study, through a combination of single B cell sequencing and next-generation sequencing analysis, we systemically studied the dynamic changes of antibody lineages derived from different B cell germlines in their sequence, frequency, and neutralization ability in different vaccinees before and after receiving inactivated SARS-CoV-2 vaccines. Our findings indicate that the frequency of antibodies derived from the IGHV4-34 lineage increased in most individuals after vaccination, and the higher frequency of the antibody usually resulted in stronger binding affinity. Additionally, the ratio of IGHV4-34 derived antibodies, when compared with other public antibodies, more strongly correlated with the neutralization activity of immune sera from vaccinees. Taken together, these results suggest that IGHV4-34 is a novel vaccine-elicited public nAb lineage that plays a crucial role in immune response following inactivated COVID-19 vaccination.