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Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination.

文献信息

DOI10.1038/s41591-021-01464-w
PMID34312554
期刊Nature medicine
影响因子50.0
JCR 分区Q1
发表年份2021
被引次数216
关键词异源疫苗接种, 免疫原性, 反应原性, T细胞, 抗体
文献类型Journal Article, Observational Study, Research Support, Non-U.S. Gov't
ISSN1078-8956
页码1530-1535
期号27(9)
作者Tina Schmidt, Verena Klemis, David Schub, Janine Mihm, Franziska Hielscher, Stefanie Marx, Amina Abu-Omar, Laura Ziegler, Candida Guckelmus, Rebecca Urschel, Sophie Schneitler, Sören L Becker, Barbara C Gärtner, Urban Sester, Martina Sester

一句话小结

本研究探讨了异源疫苗接种(ChAdOx1 nCoV-19与mRNA疫苗)在健康成年人中的免疫反应,结果显示异源接种方案能够显著提高针对刺突蛋白的IgG和中和抗体水平,以及CD4和CD8 T细胞的反应,且其耐受性良好,反应原性与同源接种相似。这一发现为异源疫苗方案在新冠疫苗接种中的应用提供了有力支持,显示出其在增强免疫应答方面的潜力。

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异源疫苗接种 · 免疫原性 · 反应原性 · T细胞 · 抗体

摘要

异源激活使用ChAdOx1 nCoV-19载体疫苗后,再进行信使RNA疫苗(BNT162b2或mRNA-1273)的加强接种,目前在德国被推荐,尽管关于免疫原性和反应原性的数据显示尚不可得。在这项观察性研究中,我们表明,在健康成年个体(n=96)中,异源疫苗方案诱导了特异性针对刺突蛋白的IgG、中和抗体和特异性针对刺突蛋白的CD4 T细胞,其水平显著高于同源载体疫苗加强接种(n=55),并且与同源mRNA疫苗方案(n=62)相比,水平相似或更高。此外,异源接种后特异性针对刺突蛋白的CD8 T细胞水平显著高于两种同源方案。所有三种方案中的特异性T细胞主要是多功能的,并且产生细胞因子的表型在很大程度上重叠。接受同源载体方案和异源载体/mRNA组合的受试者在初始载体疫苗接种后报告了更大的反应原性,而异源加强接种则耐受良好,且与同源mRNA加强接种相当。综合来看,异源载体/mRNA加强接种能引发强烈的体液和细胞免疫应答,并具有可接受的反应原性特征。

英文摘要

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

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主要研究问题

  1. 在异源疫苗接种中,如何评估不同疫苗组合的长期免疫持久性?
  2. 该研究中提到的T细胞亚群的多功能性如何影响疫苗的整体免疫效果?
  3. 针对不同年龄段或基础疾病患者,异源接种的免疫原性和反应原性是否存在显著差异?
  4. 该研究的结果如何影响未来疫苗接种策略,尤其是在变异株流行的情况下?
  5. 在异源接种中,疫苗接种后不良反应的监测与评估应该采取哪些措施以确保安全性?

核心洞察

研究背景和目的

随着COVID-19疫情的持续,疫苗接种成为控制疫情的重要手段。针对不同类型疫苗的免疫原性和反应性研究日益受到关注。本研究旨在评估异源疫苗接种方案(ChAdOx1 nCoV-19与mRNA疫苗的组合)对免疫反应的影响,以确定其有效性和安全性。

主要方法/材料/实验设计

本研究采用了多组对照设计,比较了不同接种方案下的免疫反应。研究对象分为三组:接种两剂ChAdOx1 nCoV-19疫苗(Vector/Vector)、一剂ChAdOx1 nCoV-19加一剂mRNA疫苗(Vector/mRNA)和两剂mRNA疫苗(mRNA/mRNA)。每组均评估了CD4+ T细胞、CD8+ T细胞、IgG抗体和中和抗体的产生情况。

以下是研究的技术路线图:

Mermaid diagram

关键结果和发现

  1. 免疫反应评估

    • 所有接种组均显示出良好的免疫反应,尤其是mRNA/mRNA组的中和抗体水平显著高于其他组。
    • CD4+和CD8+ T细胞的激活状态在Vector/mRNA组中表现最为明显。
  2. 反应性评估

    • 接种后的不良反应(如发热、疲劳等)在不同组别间差异不大,但Vector/mRNA组的反应性略高于其他组。
  3. 统计分析

    • 通过Spearman相关性分析,发现CD4+ T细胞与中和抗体之间存在显著正相关(R=0.421, P=0.0007)。

主要结论/意义/创新性

本研究表明,异源疫苗接种方案(ChAdOx1 nCoV-19与mRNA疫苗组合)能够有效增强免疫反应,尤其是在中和抗体的产生方面。这为疫苗接种策略的优化提供了重要的实验依据,可能为未来的疫苗接种提供新的方向。

研究局限性和未来方向

  1. 局限性

    • 研究样本量相对较小,可能影响结果的普遍性。
    • 仅在短期内评估了免疫反应,长期效果尚需进一步研究。
  2. 未来方向

    • 建议进行更大规模的临床试验,以验证异源疫苗接种的长期效果和安全性。
    • 进一步探索不同疫苗组合对不同人群的免疫反应差异,以制定个性化的疫苗接种策略。

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引用本文的文献

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