Longitudinal change trend of the TCR repertoire reveals the immune response intensity of the inactivated COVID-19 vaccine

Evidence concerning the individual differences in neutralizing antibody responses after receiving the COVID-19 vaccine remains lacking. In this study, we collected the serum and Peripheral blood mononuclear cells(PBMC) of 16 subjects who had never suffered from COVID-19 before during the course of two vaccine doses. Microneutralization assay is used to determine the immune response intensity of vaccine subjects. we revealed the change trend of TCR diversity using T cell receptor (TCR) sequencing. Then, we analyzed the correlation between HLA class II allele frequencies and the intensity of immune response. Finally, we identified several CDR3 sequences related to the intensity of the immune response. We analyzed the differences in D50 (DD50) between different time points, and found that there were two patterns in the change trend of TCR diversity, and the increased diversity group has stronger immune response. The inactivated vaccine is different from the mRNA vaccine against the spike protein, resulting in differences in TCR repertoire response patterns and antibody responses, which are related to HLA-DRB1 * 09:01. The presence of specific CDR3 sequences in the increased diversity group, rather than gene usage of the VJ gene, determines the intensity and persistence of neutralizing antibody titers. Finally, We identified the different response patterns of the human TCR repertoire to inactivated vaccines. The pattern with increased diversity is more likely to appear strong and more lasting immune response.