PT  - JOURNAL ARTICLE
AU  - Suhas Sureshchandra
AU  - Sloan A. Lewis
AU  - Brianna Doratt
AU  - Allen Jankeel
AU  - Izabela Ibraim
AU  - Ilhem Messaoudi
TI  - Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine
AID  - 10.1101/2021.07.14.452381
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.14.452381
4099  - http://biorxiv.org/content/early/2021/07/15/2021.07.14.452381.short
4100  - http://biorxiv.org/content/early/2021/07/15/2021.07.14.452381.full
AB  - mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used single-cell RNA sequencing and functional assays to compare humoral and cellular responses to two doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4 T cells, and robust antigen-specific polyfunctional CD4 T cell responses in all vaccinees. On the other hand, CD8 T cell responses were both weak and variable. Interestingly, clonally expanded CD8 T cells were observed in every vaccinee, as observed following natural infection. TCR gene usage, however, was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of larger CD8 T cell clones occupied distinct clusters, likely due to the recognition of a broader set of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response where early CD4 T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8 T cells, together capable of contributing to future recall responses.Competing Interest StatementThe authors have declared no competing interest.