Proteomic and Cellular Characterization of Omicron Breakthrough Infections and a Third Homologous or Heterologous Boosting Vaccination in a Longitudinal Cohort.

IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Molecular & Cellular Proteomics Pub Date : 2024-06-01 Epub Date: 2024-04-18 DOI:10.1016/j.mcpro.2024.100769
Yi Zhang, Zhangfan Fu, Haocheng Zhang, Ke Lin, Jieyu Song, Jingxin Guo, Qiran Zhang, Guanmin Yuan, Hongyu Wang, Mingxiang Fan, Yuanhan Zhao, Rui Sun, Tiannan Guo, Ning Jiang, Chao Qiu, Wenhong Zhang, Jingwen Ai
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Abstract

The understanding of dynamic plasma proteome features in hybrid immunity and breakthrough infection is limited. A deeper understanding of the immune differences between heterologous and homologous immunization could assist in the future establishment of vaccination strategies. In this study, 40 participants who received a third dose of either a homologous BBIBP-CorV or a heterologous ZF2001 protein subunit vaccine following two doses of inactivated coronavirus disease 2019 vaccines and 12 patients with BA2.2 breakthrough infections were enrolled. Serum samples were collected at days 0, 28, and 180 following the boosting vaccination and breakthrough and then analyzed using neutralizing antibody tests and mass spectrometer-based proteomics. Mass cytometry of peripheral blood mononuclear cell samples was also performed in this cohort. The chemokine signaling pathway and humoral response markers (IgG2 and IgG3) associated with infection were found to be upregulated in breakthrough infections compared to vaccination-induced immunity. Elevated expression of IGKV, IGHV, IL-17 signaling, and the phagocytosis pathway, along with lower expression of FGL2, were correlated with higher antibody levels in the boosting vaccination groups. The MAPK signaling pathway and Fc gamma R-mediated phagocytosis were more enriched in the heterologous immunization groups than in the homologous immunization groups. Breakthrough infections can trigger more intensive inflammatory chemokine responses than vaccination. T-cell and innate immune activation have been shown to be closely related to enhanced antibody levels after vaccination and therefore might be potential targets for vaccine adjuvant design.

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纵向队列中 Omicron 突破性感染和第三次同源或异源强化疫苗接种的蛋白质组和细胞特征。
背景:人们对混合免疫和突破性感染中血浆蛋白质组的动态特征了解有限。深入了解异源免疫和同源免疫之间的免疫差异有助于未来制定疫苗接种策略:在这项研究中,40 名参与者在接种了两剂 2019 年冠状病毒病灭活疫苗后,又接种了第三剂同源 BBIBP-CorV 或异源 ZF2001 蛋白亚单位疫苗,还有 12 名 BA.2.2 突破性感染患者。在加强免疫和突破感染后的第 0、28 和 180 天采集血清样本,然后使用中和抗体测试和基于质谱仪的蛋白质组学进行分析。此外,还对外周血单核细胞样本进行了质谱分析:结果:与疫苗接种诱导的免疫力相比,突破性感染中与感染相关的趋化因子信号通路和体液反应标记物(IgG2 和 IgG3)被上调。在加强免疫组中,IGKV、IGHV、IL-17 信号通路和吞噬通路表达的升高以及 FGL2 表达的降低与较高的抗体水平相关。与同源免疫组相比,异源免疫组的MAPK信号通路和Fc gamma R介导的吞噬作用更为丰富:结论:与接种疫苗相比,突破性感染可引发更强烈的炎症趋化因子反应。T细胞和先天性免疫激活已被证明与疫苗接种后抗体水平的提高密切相关,因此可能成为疫苗佐剂设计的潜在目标。
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来源期刊
Molecular & Cellular Proteomics
Molecular & Cellular Proteomics 生物-生化研究方法
CiteScore
11.50
自引率
4.30%
发文量
131
审稿时长
84 days
期刊介绍: The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes
期刊最新文献
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