Comprehensive comparison of adaptive immune responses to inactivated SARS-CoV-2 vaccine between young and old

Abstract Aging is a critical risk factor for SARS-CoV-2 vaccine efficacy. Although low humoral immunity in the elderly was observed in mRNA and recombinant protein vaccination, it is still unclear how inactivated SARS-CoV-2 vaccine stimulates humoral and cellular immunity in elderly in the real world. Here, combining neutralizing antibody, tetramer stained CD8 T cells, transcriptome, and single cell TCR-seq examinations, we comprehensively compared immune responses before and after inactivated SARS-CoV-2 vaccination between 121 young and 48 old donors. Our data demonstrated that the inactivated SARS-CoV-2 vaccine can successfully induce antibody and T cells responses in the old people, although the responses were slower and weaker than young adults. The mechanism of impaired immune responses in elderly is likely due to altered immune cell function and decreased BCR and TCR repertoire diversity. In addition, impaired immune response due to mutant epitopes from SARS-CoV-2 variants raises concerns for future vaccine design. This work was supported by grants from the National Key Research and Development Program of China (2018YFC2002003 to G.C., 2021YFC2009400 to G.Z.), the Natural Science Foundation of China (U1801285 to G.C., 81971301 and 32050410285 to O.J.L.)