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第三剂 COVID-19 mRNA 疫苗接种后针对奥密克戎变异株的持续 T 细胞介导的免疫应答。

Persistent T cell-mediated immune responses against Omicron variants after the third COVID-19 mRNA vaccine dose.

机构信息

Institute of Biomedicine, University of Turku, Turku, Finland.

Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland.

出版信息

Front Immunol. 2023 Jan 23;14:1099246. doi: 10.3389/fimmu.2023.1099246. eCollection 2023.


DOI:10.3389/fimmu.2023.1099246
PMID:36756112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9899862/
Abstract

INTRODUCTION: The prime-boost COVID-19 mRNA vaccination strategy has proven to be effective against severe COVID-19 disease and death. However, concerns have been raised due to decreasing neutralizing antibody levels after COVID-19 vaccination and due to the emergence of new immuno-evasive SARS-CoV-2 variants that may require additional booster vaccinations. METHODS: In this study, we analyzed the humoral and cell-mediated immune responses against the Omicron BA.1 and BA.2 subvariants in Finnish healthcare workers (HCWs) vaccinated with three doses of COVID-19 mRNA vaccines. We used enzyme immunoassay and microneutralization test to analyze the levels of SARS-CoV-2 specific IgG antibodies in the sera of the vaccinees and the in vitro neutralization capacity of the sera. Activation induced marker assay together with flow cytometry and extracellular cytokine analysis was used to determine responses in SARS-CoV-2 spike protein stimulated PBMCs. RESULTS: Here we show that within the HCWs, the third mRNA vaccine dose recalls both humoral and T cell-mediated immune responses and induces high levels of neutralizing antibodies against Omicron BA.1 and BA.2 variants. Three weeks after the third vaccine dose, SARS-CoV-2 wild type spike protein-specific CD4 and CD8 T cells are observed in 82% and 71% of HCWs, respectively, and the T cells cross-recognize both Omicron BA.1 and BA.2 spike peptides. Although the levels of neutralizing antibodies against Omicron BA.1 and BA.2 decline 2.5 to 3.8-fold three months after the third dose, memory CD4 T cell responses are maintained for at least eight months post the second dose and three months post the third vaccine dose. DISCUSSION: We show that after the administration of the third mRNA vaccine dose the levels of both humoral and cell-mediated immune responses are effectively activated, and the levels of the spike-specific antibodies are further elevated compared to the levels after the second vaccine dose. Even though at three months after the third vaccine dose antibody levels in sera decrease at a similar rate as after the second vaccine dose, the levels of spike-specific CD4 and CD8 T cells remain relatively stable. Additionally, the T cells retain efficiency in cross-recognizing spike protein peptide pools derived from Omicron BA.1 and BA.2 subvariants. Altogether our results suggest durable cellmediated immunity and protection against SARS-CoV-2.

摘要

简介:COVID-19 mRNA 疫苗的初级-加强免疫策略已被证明能有效预防 COVID-19 重症和死亡。然而,由于 COVID-19 疫苗接种后中和抗体水平下降,以及可能需要额外加强针的新型免疫逃避 SARS-CoV-2 变异株出现,人们对此表示担忧。

方法:本研究分析了接种三剂 COVID-19 mRNA 疫苗的芬兰医护人员对奥密克戎 BA.1 和 BA.2 亚变异株的体液和细胞介导免疫反应。我们使用酶免疫测定法和微量中和试验分析疫苗接种者血清中的 SARS-CoV-2 特异性 IgG 抗体水平,以及血清的体外中和能力。激活诱导标志物分析联合流式细胞术和细胞外细胞因子分析用于确定 SARS-CoV-2 刺突蛋白刺激 PBMC 中的反应。

结果:在此,我们表明在医护人员中,第三剂 mRNA 疫苗可同时召回体液和 T 细胞介导的免疫反应,并诱导针对奥密克戎 BA.1 和 BA.2 变异株的高水平中和抗体。第三剂疫苗接种后 3 周,分别有 82%和 71%的医护人员观察到 SARS-CoV-2 野生型刺突蛋白特异性 CD4 和 CD8 T 细胞,且 T 细胞交叉识别奥密克戎 BA.1 和 BA.2 刺突肽。尽管第三剂疫苗接种后 3 个月,针对奥密克戎 BA.1 和 BA.2 的中和抗体水平下降 2.5 至 3.8 倍,但记忆性 CD4 T 细胞反应至少在第二剂疫苗接种后 8 个月和第三剂疫苗接种后 3 个月内保持。

讨论:我们表明,第三剂 mRNA 疫苗接种后,体液和细胞介导的免疫反应均有效激活,且与第二剂疫苗接种后相比,刺突特异性抗体水平进一步升高。尽管第三剂疫苗接种后 3 个月,血清中抗体水平下降速度与第二剂疫苗接种后相似,但刺突特异性 CD4 和 CD8 T 细胞水平仍相对稳定。此外,T 细胞仍能有效地交叉识别来自奥密克戎 BA.1 和 BA.2 亚变异株的刺突蛋白肽库。总之,我们的结果表明了持久的细胞介导免疫和对 SARS-CoV-2 的保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/541dc0db2d90/fimmu-14-1099246-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/f18b6ea8f091/fimmu-14-1099246-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/50f759276caf/fimmu-14-1099246-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/a18a256acf2c/fimmu-14-1099246-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/a2266d0ab412/fimmu-14-1099246-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/481929c64d67/fimmu-14-1099246-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/541dc0db2d90/fimmu-14-1099246-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/f18b6ea8f091/fimmu-14-1099246-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/50f759276caf/fimmu-14-1099246-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/a18a256acf2c/fimmu-14-1099246-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/a2266d0ab412/fimmu-14-1099246-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/481929c64d67/fimmu-14-1099246-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378f/9899862/541dc0db2d90/fimmu-14-1099246-g006.jpg

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