Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses.

IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-11-09 DOI:10.1016/j.ebiom.2024.105438
Sebastian Einhauser, Claudia Asam, Manuela Weps, Antonia Senninger, David Peterhoff, Stilla Bauernfeind, Benedikt Asbach, George William Carnell, Jonathan Luke Heeney, Monika Wytopil, André Fuchs, Helmut Messmann, Martina Prelog, Johannes Liese, Samuel D Jeske, Ulrike Protzer, Michael Hoelscher, Christof Geldmacher, Klaus Überla, Philipp Steininger, Ralf Wagner
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Abstract

Background: The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study.

Methods: 173 vaccinated and 56 non-vaccinated individuals were enrolled after SARS-CoV-2 Alpha, Delta, or Omicron infection and visited four times within 6 months and nAbs were measured for D614G, Alpha, Delta, BA.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and JN.1.

Findings: Magnitude-breadth-analysis showed enhanced neutralization capacity in vaccinated individuals against multiple VOCs. Longitudinal analysis revealed sustained neutralization magnitude-breadth after antigenically distant Delta or Omicron breakthrough infection (BTI), with triple-vaccinated individuals showing significantly elevated titres and improved breadth. Antigenic mapping and antibody landscaping revealed initial boosting of vaccine-induced WT-specific responses after BTI, a shift in neutralization towards infecting VOCs at peak responses and an immune imprinted bias towards dominating WT immunity in the long-term. Despite that bias, machine-learning models confirmed a sustained shift of the immune-profiles following BTI.

Interpretation: In summary, our longitudinal analysis revealed delayed and short lived nAb shifts towards the infecting VOC, but an immune imprinted bias towards long-term vaccine induced immunity after BTI.

Funding: This work was funded by the Bavarian State Ministry of Science and the Arts for the CoVaKo study and the ForCovid project. The funders had no influence on the study design, data analysis or data interpretation.

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SARS-CoV-2 突破性感染对中和抗体反应印记的纵向影响。
背景:方法:在SARS-CoV-2 Alpha、Delta或Omicron感染后登记了173名已接种疫苗的个体和56名未接种疫苗的个体,并在6个月内进行了4次访视,测量了D614G、Alpha、Delta、BA.1、BA.2、BA.5、BQ.1.1、XBB.1.5和JN.1的nAb、BA.2、BA.5、BQ.1.1、XBB.1.5 和 JN.1.Findings 的 nAbs:幅度-广度分析表明,接种疫苗的人对多种挥发性有机化合物的中和能力增强。纵向分析表明,在抗原距离较远的德尔塔或奥米克隆突破性感染(BTI)后,中和幅度-广度保持不变,接种三联疫苗的个体滴度明显升高,广度也有所提高。抗原图谱和抗体图谱显示,在 BTI 之后,疫苗诱导的 WT 特异性反应开始增强,在高峰反应时,中和作用转向感染 VOC,而在长期免疫中,免疫印记偏向于主导 WT 免疫。尽管存在这种偏差,但机器学习模型证实了 BTI 之后免疫特征的持续转变:总之,我们的纵向分析表明,nAb向感染性VOC的转移具有延迟性和短暂性,但免疫印记偏向于BTI后的长期疫苗诱导免疫:本研究由巴伐利亚州科学与艺术部资助,用于CoVaKo研究和ForCovid项目。资助方对研究设计、数据分析或数据解释没有任何影响。
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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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