Ebola virus antibody decay-stimulation in a high proportion of survivors.

Ebola virus antibody decay-stimulation in a high proportion of survivors.
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DOI:
10.1038/s41586-020-03146-y
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发表时间:
2021-03
期刊:
影响因子:
64.8
通讯作者:
Pollakis G
Pollakis G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Adaken C;Scott JT;Sharma R;Gopal R;Dicks S;Niazi S;Ijaz S;Edwards T;Smith CC;Cole CP;Kamara P;Kargbo O;Doughty HA;van Griensven J;Horby PW;Gevao SM;Sahr F;Ebola-CP Consortium;Dimelow RJ;Tedder RS;Semple MG;Paxton WA;Pollakis G

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中和抗体功能为疫苗和疗法的功效提供了基础。在这里,使用一种强大的体外埃博拉病毒(EBOV)假颗粒感染检测和一组定义明确的固相检测,我们描述了2013-2016年塞拉利昂EBOV疫情健康幸存者队列中的广泛抗体应答。假颗粒病毒中和抗体与总抗EBOV反应性和针对活EBOV的中和抗体相关。类似地中和变体EBOV糖蛋白(1995和2014菌株)。在纵向随访期间,抗体应答以“衰减-刺激-衰减”模式波动,表明恢复后EBOV抗原重新刺激。抗体反应性的药效学模型确定了77-100天的衰变半衰期和46-86天的倍增时间在高比例的幸存者。在个体恢复后约200天观察到最高抗体反应性。该模型表明EBOV抗体反应性在恢复后0.5-2年内下降。在高比例的健康幸存者中,抗体反应经历快速再刺激。应考虑对幸存者进行警惕随访,并通过疫苗免疫进行可能的选择性从头抗原刺激,以防止EBOV病毒在恢复个体中复发,从而减轻重新接种暴发的潜在风险。在许多埃博拉病毒感染的幸存者中,抗体反应显示出长期的下降模式,随后是重新刺激,这可能是由于持续存在的病毒复发。
Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013–2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a ‘decay–stimulation–decay’ pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77–100 days and a doubling time of 46–86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak. In many survivors of Ebola virus infection, antibody responses show long-term patterns of decline followed by restimulation, possibly owing to recrudescence of persisting virus.
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发表时间: 2015
期刊: The journal of venomous animals and toxins including tropical diseases
影响因子: --
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