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Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine
Suhas Sureshchandra, … , Izabela Coimbra Ibraim, Ilhem Messaoudi
Suhas Sureshchandra, … , Izabela Coimbra Ibraim, Ilhem Messaoudi
Published December 22, 2021
Citation Information: JCI Insight. 2021;6(24):e153201. https://doi.org/10.1172/jci.insight.153201.
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Research Article COVID-19 Vaccines

Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

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Abstract

mRNA 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 scRNA-Seq and functional assays to compare humoral and cellular responses to 2 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 following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which 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.

Authors

Suhas Sureshchandra, Sloan A. Lewis, Brianna M. Doratt, Allen Jankeel, Izabela Coimbra Ibraim, Ilhem Messaoudi

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Figure 1

Immunological changes with SARS-CoV-2 mRNA vaccination.

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Immunological changes with SARS-CoV-2 mRNA vaccination.
(A) Experimental...
(A) Experimental design for the study. Blood was collected from SARS-CoV-2–naive individuals before vaccination, 2 weeks after dose 1, and 2 weeks after prime-boost vaccination (VACC group) or in SARS-CoV-2–exposed but asymptomatic individuals (CONV group) before and after convalescence. Immune phenotypes of PBMCs and antigen-specific T and B cell responses were measured using multicolor flow cytometry. Longitudinal serological responses to the vaccine were measured using ELISA and neutralization assays. Memory T and B cells from a subset of PBMC samples (n = 4/group for vaccine volunteers, n = 3/group for convalescent health care workers, matched) were profiled using scRNA-Seq at baseline (before vaccination) or after vaccination time points. (B) UMAP projection of 32,867 memory T and B cells with major subsets annotated. (C) Violin plots of key gene markers used for cluster annotations. Normalized transcript counts are shown on the y axis.

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