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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1460442

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

Provisionally accepted
Yuwei Zhang Yuwei Zhang 1Shanshan Han Shanshan Han 2*Qingshuai Sun Qingshuai Sun 2*Tao Liu Tao Liu 3Zixuan Wen Zixuan Wen 4Mingxiao Yao Mingxiao Yao 1*Shu Zhang Shu Zhang 1Qing Duan Qing Duan 1Xiaomei Zhang Xiaomei Zhang 1*Bo Pang Bo Pang 1Zengqiang Kou Zengqiang Kou 1*Xiaolin Jiang Xiaolin Jiang 1*
  • 1 Shandong Center for Disease Control and Prevention, Shandong, China
  • 2 School of Public Health and Health Management, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
  • 3 Yantai Disease Prevention and Control Center, Yantai, Shandong Province, China
  • 4 School of Public Health, Weifang Medical University, Weifang, China

The final, formatted version of the article will be published soon.

    The high percentage of Omicron breakthrough infection in vaccinees is an emerging problem, of which we have a limited understanding of the phenomenon. We 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 naï ve with booster vaccination. We 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 proinflammatoryrelated 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. Collectively, 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.

    Keywords: COVID-19, omicron, Booster vaccination, Breakthrough infection, ScRNA-seq, peripheral immune responses

    Received: 06 Jul 2024; Accepted: 13 Dec 2024.

    Copyright: © 2024 Zhang, Han, Sun, Liu, Wen, Yao, Zhang, Duan, Zhang, Pang, Kou and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Shanshan Han, School of Public Health and Health Management, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
    Qingshuai Sun, School of Public Health and Health Management, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
    Mingxiao Yao, Shandong Center for Disease Control and Prevention, Shandong, China
    Xiaomei Zhang, Shandong Center for Disease Control and Prevention, Shandong, China
    Zengqiang Kou, Shandong Center for Disease Control and Prevention, Shandong, China
    Xiaolin Jiang, Shandong Center for Disease Control and Prevention, Shandong, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.