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[转载]外周血中和抗体水平与新冠疫苗保护率Correlates of protection against SARS-CoV-2

已有 1910 次阅读 2021-7-14 23:28 |系统分类:论文交流|文章来源:转载

  2021年6 月 24 日,来自牛津大学和阿斯利康(AstraZeneca)开发新冠疫苗的研究团队的 全球首个新冠疫苗免疫学保护相关性指标的研究 发表在预印本平台 medRxiv,为之后设定新冠疫苗的免疫学替代终点提供了重要基础,同时也回答了两个至关重要的问题:

1. 接种新冠疫苗之后,我该如何确认自己是否受到有效保护?

2. 新的新冠疫苗,怎样才能不做 III 期试验就尽快明确有效率?

   牛津大学研究团队通过测定 1500 多名疫苗接种者的抗体水平,再持续监测这些人后续被感染的情况,从而确定中和抗体水平与疫苗保护作用的关系


   受试者是牛津/阿斯利康新冠疫苗在英国的 III 期试验 COV002 的一部分,实验组 4369 人接种了两剂阿斯利康黑猩猩腺病毒疫苗,安慰剂组 4194 人接种 MenACWY 流脑疫苗。这部分受试者在接种第二针 28 天后采血检测抗体,之后每周进行一次核酸检测,持续检测 6 个月。

    核酸阳性的受试者按照疾病症状分为有症状感染(出现发热、咳嗽、疲劳、失去嗅觉味觉和呼吸困难中的至少一项)、非主要症状感染(有症状但不是上述五种)和无症状感染。受试者超过六成是医护人员。

    结果显示,6 个月内牛津/阿斯利康新冠疫苗对有常见症状感染的有效率是 73.1%,抗无症状感染的有效率为 15.1%,这些数据与阿斯利康其它几个 III 期临床试验的结果基本吻合。


   而这项研究最为重要的目的,是探究外周血中和抗体与疫苗有效率的关系


    研究测定了其中 1500 余名接种者的抗体水平,然后分别统计他们的感染率,计算不同抗体水平的感染风险和疫苗保护效力,结果表明,接种疫苗后仍被感染(也就是发生了疫苗突破性感染)的人群确实是接种组中水平较低的部分。

    研究结果显示,接种疫苗后,抗 Spike 抗体高于 40923AU/ml,或者活病毒中和实验滴度高于 247,接种者的感染风险就会降低至安慰剂组的 20%,也就是说,疫苗有效率达到了 80%接种疫苗后,抗 Spike 抗体高于 4446AU/ml,或者活病毒中和抗体滴度能超过 68,则疫苗有效率将达到 50%。


    PS: 目前大部分疫苗都以外周血抗体水平作为「免疫学保护相关性指标」。最常见的是接种乙肝疫苗后检测抗 HBs 抗体,达到 10mIU/ml 即视为有效;而流感疫苗是以血凝抑制抗体滴度 40 为阈值。
    以上转自丁香园   作者 王瀚

AU/mL values for anti-spike IgG and anti-RBD IgG can be converted to the WHO international standard (NIBSC code 20/136) using the following conversion factors: Spike: BAU/mL = AU/mL x 0.00645 RBD: BAU/mL = AU/mL x 0.00798. BAU/ml: Binding antibody units per millilitre.

抗体水平.jpg
Relative risk of primary symptomatic COVID-19 among vaccine recipients compared with MenACWY control arm participants as a function of immune markers measured at day 28 post-second dose.

(Red shaded areas represent the immune marker density distribution. Green lines show the relative risk of infection among vaccine recipients compared to the MenACWY control arm participants. Green shaded areas are 95% bootstrapped confidence intervals for the relative risk. The arrows point to the immune marker values at 20% and 50% relative risk, i.e., 80% and 50% vaccine efficacy for illustrative purpose.)


疫苗保护率.jpg

    Vaccine efficacy against primary symptomatic COVID-19 as a function of immune markers measured at day 28 post-second dose.

(Red shaded areas represent the immune marker density distribution. Green lines show the vaccine efficacy and green dotted lines are 95% bootstrapped confidence intervals for vaccine efficacy.)

    这是全球第一个关于新冠疫苗免疫学保护相关性指标的研究,尽管还没有经过同行评议正式发表,但 Nature 杂志已对此进行了报道和讨论。

Callaway, E. (2021). Scientists identify long-sought marker for COVID vaccine success. Nature.

https://www.nature.com/articles/d41586-021-01778-2

    Researchers developing the Oxford–AstraZeneca COVID-19 vaccine have identified biomarkers that can help to predict whether someone will be protected by the jab they receive.


The team at the University of Oxford, UK, identified a ‘correlate of protection’ from the immune responses of trial participants — the first found by any COVID-19 vaccine developer. Identifying such blood markers, scientists say, will improve existing vaccines and speed the development of new ones by reducing the need for costly large-scale efficacy trials.


“We would like to have an antibody measure that is a reliable guide to protection because it could speed up the licensure of new vaccines,” says David Goldblatt, a vaccinologist at University College London.

 ...

These studies suggest that virus-blocking ‘neutralizing’ antibodies are a good predictor of a vaccine’s success. Those that trigger high levels of these antibodies, such as the Pfizer–BioNTech and Moderna jabs, are more effective than the Oxford–AstraZeneca and Johnson & Johnson vaccines, which generated relatively low levels of neutralizing antibodies. 

研究人员确认,能够识别新冠病毒刺突蛋白、识别刺突蛋白RBD并与之结合的IgG抗体水平越高,中和性抗体滴度越高 的参与者,往往能获得更强的保护,预防有症状感染。研究人员补充说,这一结果将免疫反应与接种后预期的人群保护关联起来,但并不能用于检查个人在接种疫苗后获得的保护。

Nature更多讨论详见:doi: https://doi.org/10.1038/d41586-021-01778-2


原文摘要:

Abstract

Background: Although 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16th June 2021, global supply remains limited. An understanding of the immune response associated with protection could facilitate rapid licensure of new vaccines.


Methods: Data from a randomised efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analysed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralising antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalised additive models for binary data were applied to symptomatic and asymptomatic SARS-CoV-2 infection data from ChAdOx1 nCoV-19 recipients. Cubic spline smoothed log antibody levels, and weights were applied to account for potential selection bias in sample processing. Models were adjusted for baseline risk of exposure to SARS-CoV-2 infection.


Results: Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with an antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection.


Conclusions Correlates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.


参考文献:

Feng, S., Phillips, D. J., White, T., Sayal, H., Aley, P. K., Bibi, S., ... & Oxford COVID Vaccine Trial Group. (2021). Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. medRxiv.

doi: https://doi.org/10.1101/2021.06.21.21258528

https://www.medrxiv.org/content/10.1101/2021.06.21.21258528v1





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