Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies

IntroductionThe high percentage of Omicron breakthrough infection in vaccinees is an emerging problem, of which we have a limited understanding of the phenomenon.MethodsWe performed single-cell transcriptome coupled with T-cell/B-cell receptor (TCR/BCR) sequencing in 15 peripheral blood mononuclear...

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Main Authors: Yuwei Zhang, Shanshan Han, Qingshuai Sun, Tao Liu, Zixuan Wen, Mingxiao Yao, Shu Zhang, Qing Duan, Xiaomei Zhang, Bo Pang, Zengqiang Kou, Xiaolin Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1460442/full
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author Yuwei Zhang
Shanshan Han
Qingshuai Sun
Tao Liu
Zixuan Wen
Mingxiao Yao
Shu Zhang
Qing Duan
Xiaomei Zhang
Bo Pang
Zengqiang Kou
Xiaolin Jiang
Xiaolin Jiang
Xiaolin Jiang
author_facet Yuwei Zhang
Shanshan Han
Qingshuai Sun
Tao Liu
Zixuan Wen
Mingxiao Yao
Shu Zhang
Qing Duan
Xiaomei Zhang
Bo Pang
Zengqiang Kou
Xiaolin Jiang
Xiaolin Jiang
Xiaolin Jiang
author_sort Yuwei Zhang
collection DOAJ
description IntroductionThe high percentage of Omicron breakthrough infection in vaccinees is an emerging problem, of which we have a limited understanding of the phenomenon.MethodsWe performed single-cell transcriptome coupled with T-cell/B-cell receptor (TCR/BCR) sequencing in 15 peripheral blood mononuclear cell (PBMC) samples from Omicron infection and naïve with booster vaccination.ResultsWe found that after breakthrough infection, multiple cell clusters showed activation of the type I IFN pathway and widespread expression of Interferon-stimulated genes (ISGs); T and B lymphocytes exhibited antiviral and proinflammatory-related differentiation features with pseudo-time trajectories; and large TCR clonal expansions were concentrated in effector CD8 T cells, and clonal expansions of BCRs showed a preference for IGHV3. In addition, myeloid cells in the BA.5.2 breakthrough infection with the fourth dose of aerosolized Ad5-nCoV were characterized by enhanced proliferation, chemotactic migration, and antigen presentation.DiscussionCollectively, our study informs the comprehensive understandings of immune characterization for Omicron breakthrough infection, revealing the positive antiviral potential induced by booster doses of vaccine and the possible "trained immunity" phenomenon in the fourth dose of aerosolized Ad5-nCoV, providing a basis for the selection of vaccination strategies.
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publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-666cf2f9c6ff429c8326da64cf6e66652025-01-06T06:59:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14604421460442Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategiesYuwei Zhang0Shanshan Han1Qingshuai Sun2Tao Liu3Zixuan Wen4Mingxiao Yao5Shu Zhang6Qing Duan7Xiaomei Zhang8Bo Pang9Zengqiang Kou10Xiaolin Jiang11Xiaolin Jiang12Xiaolin Jiang13Infectious Disease Prevention and Control Section, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaSchool of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaSchool of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaDepartment of Infectious Disease Control, Yantai Center for Disease Control and Prevention, Yantai, Shandong, ChinaSchool of Public Health, Weifang Medical University, Weifang, Shandong, ChinaInfectious Disease Prevention and Control Section, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaInfectious Disease Prevention and Control Section, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaInfectious Disease Prevention and Control Section, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaInfectious Disease Prevention and Control Section, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaInfectious Disease Prevention and Control Section, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaInfectious Disease Prevention and Control Section, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaSchool of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaSchool of Public Health, Weifang Medical University, Weifang, Shandong, ChinaShandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, Shandong, ChinaIntroductionThe high percentage of Omicron breakthrough infection in vaccinees is an emerging problem, of which we have a limited understanding of the phenomenon.MethodsWe performed single-cell transcriptome coupled with T-cell/B-cell receptor (TCR/BCR) sequencing in 15 peripheral blood mononuclear cell (PBMC) samples from Omicron infection and naïve with booster vaccination.ResultsWe found that after breakthrough infection, multiple cell clusters showed activation of the type I IFN pathway and widespread expression of Interferon-stimulated genes (ISGs); T and B lymphocytes exhibited antiviral and proinflammatory-related differentiation features with pseudo-time trajectories; and large TCR clonal expansions were concentrated in effector CD8 T cells, and clonal expansions of BCRs showed a preference for IGHV3. In addition, myeloid cells in the BA.5.2 breakthrough infection with the fourth dose of aerosolized Ad5-nCoV were characterized by enhanced proliferation, chemotactic migration, and antigen presentation.DiscussionCollectively, our study informs the comprehensive understandings of immune characterization for Omicron breakthrough infection, revealing the positive antiviral potential induced by booster doses of vaccine and the possible "trained immunity" phenomenon in the fourth dose of aerosolized Ad5-nCoV, providing a basis for the selection of vaccination strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1460442/fullCOVID-19Omicronbooster vaccinationbreakthrough infectionscRNA-seqperipheral immune responses
spellingShingle Yuwei Zhang
Shanshan Han
Qingshuai Sun
Tao Liu
Zixuan Wen
Mingxiao Yao
Shu Zhang
Qing Duan
Xiaomei Zhang
Bo Pang
Zengqiang Kou
Xiaolin Jiang
Xiaolin Jiang
Xiaolin Jiang
Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies
Frontiers in Immunology
COVID-19
Omicron
booster vaccination
breakthrough infection
scRNA-seq
peripheral immune responses
title Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies
title_full Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies
title_fullStr Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies
title_full_unstemmed Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies
title_short Single-cell transcriptome atlas of peripheral immune features to Omicron breakthrough infection under booster vaccination strategies
title_sort single cell transcriptome atlas of peripheral immune features to omicron breakthrough infection under booster vaccination strategies
topic COVID-19
Omicron
booster vaccination
breakthrough infection
scRNA-seq
peripheral immune responses
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1460442/full
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