Characterizing the cellular and molecular variabilities of peripheral immune cells in healthy recipients of BBIBP-CorV inactivated SARS-CoV-2 vaccine by single-cell RNA sequencing

ABSTRACT

Over 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Our analysis revealed an enrichment of monocytes, central memory CD4⁺ T cells, type 2 helper T cells and memory B cells following vaccination. Single-cell TCR-seq and RNA-seq comminating analysis identified a clonal expansion of CD4⁺ T cells (but not CD8⁺ T cells) following a booster vaccination that corresponded to a decrease in the TCR diversity of central memory CD4⁺ T cells and type 2 helper T cells. Importantly, these TCR repertoire changes and CD4⁺ T cell differentiation were correlated with the biased VJ gene usage of BCR and the antibody-producing function of B cells post-vaccination. Finally, we compared the functional transcription and repertoire dynamics in immune cells elicited by vaccination and SARS-CoV-2 infection to explore the immune responses under different stimuli. Our data provide novel molecular and cellular evidence for the CD4⁺ T cell-dependent antibody response induced by inactivated vaccine BBIBP-CorV. This information is urgently needed to develop new prevention and control strategies for SARS-CoV-2 infection. (ClinicalTrials.gov Identifier: NCT04871932).

KEYWORDS:

• Inactivated SARS-CoV-2 vaccine
• BBIBP-CorV
• single-cell RNA sequencing
• single-cell TCR/BCR sequencing
• peripheral blood mononuclear cells

Acknowledgements

We thank the volunteers for their contribution to this study.

Author contributions

J.P and F.W conceived the study. Z.L, L.Y.S, Y.Y.L, L.H, X.G, Q.L, T.S, C.J.Z and A.C.Y recruited volunteers. R.Y.T, Y.F.C and J.F.S collected the samples from donors. R.Y.T and L.H.H conducted the experiments. R.Y.T, L.J.L, J.M.Z, L.R.H and W.L conducted the data analysis. T.R.Y, L.J.L, Y.C.Z and C.Y.F drafted the initial version of the manuscript. J.P, F.W, A.Y.C, L.C and K.Q provided constructive comments on the final version of the manuscript. All authors read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from the National Key Research and Development program of China (2021YFC2502300, 2022YFE0103500), National Natural Science Foundation of China (81500221,82071852 and 82003013), Innovative Research Team of high-level local universities in Shanghai (SHSMU-ZDCX20212100, SHSMU-ZDCX20210601), Shanghai Clinical Research Center for Aging and Medicine (19MC1910500), Science and Technology Commission of Shanghai Municipality (22QA1405400, 22DZ2292400), Shanghai Municipal Health Commission (2022JC013), Shanghai Cancer Institute (ZZ-20-22SYL).