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绝对浓度估计 COVID-19 恢复期和接种疫苗后 IgG 抗体。

Absolute concentration estimation of COVID-19 convalescent and post-vaccination IgG antibodies.

机构信息

Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States of America.

Carterra, Inc., Salt Lake City, UT, United States of America.

出版信息

PLoS One. 2024 Nov 1;19(11):e0311777. doi: 10.1371/journal.pone.0311777. eCollection 2024.

Abstract

Soon after commencement of the SARS-CoV-2 disease outbreak of 2019 (COVID-19), it became evident that the receptor-binding domain of the viral spike protein is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. This study addresses the relative lack of information regarding actual antibody concentrations and binding affinities in convalescent plasma (CP) samples from COVID-19 patients and extends these analyses to post-vaccination (PV) samples to estimate protective IgG antibody (Ab) levels. A direct enzyme-linked immunosorbent assay (ELISA) was used to measure IgG anti-spike protein (SP) antibodies (Abs) relative to human chimeric spike S1 Ab standards. Microplate wells were coated with recombinant SP. Affinities of Ab binding to SP were determined by previously described methods. Binding affinities were also determined in an RBD-specific sandwich ELISA. Two indices of protective immunity were determined as permutations of Ab molar concentration divided by affinity as dissociation constant (KD). The range and geometric means of Ab concentrations in 21 CP and 21 PV samples were similar and a protective Ab level of 7.5 μg/ml was determined for the latter population, based on 95% of the normal distribution of the PV population. A population (n = 21) of plasma samples from individuals receiving only one vaccination with the BNT162b2 or mRNA-1273 vaccines (PtV) exhibited a geometric mean Ab concentration significantly (p < 0.03) lower than the PV population. The results of this study have implications for future vaccine development, projection of protective efficacy duration, and understanding of the immune response to SARS-CoV-2 infection.

摘要

2019 年严重急性呼吸综合征冠状病毒 2 型疾病(COVID-19)爆发后不久,人们明显发现病毒刺突蛋白的受体结合域是中和抗体的靶标,中和抗体是对病毒产生保护性免疫的关键要素。本研究旨在解决 COVID-19 患者恢复期血浆(CP)样本中实际抗体浓度和结合亲和力信息相对缺乏的问题,并将这些分析扩展到疫苗接种后(PV)样本,以估计保护性 IgG 抗体(Ab)水平。本研究采用直接酶联免疫吸附测定(ELISA),用人嵌合 Spike S1 Ab 标准品来相对测量 IgG 抗刺突蛋白(SP)抗体(Abs)。微板孔用重组 SP 包被。Ab 与 SP 的结合亲和力通过之前描述的方法确定。在 RBD 特异性夹心 ELISA 中也确定了 Ab 结合的亲和力。保护性免疫的两个指标是 Ab 摩尔浓度除以亲和力(即解离常数(KD))的排列组合。21 份 CP 和 21 份 PV 样本的 Ab 浓度范围和几何平均值相似,基于 PV 人群的正态分布的 95%,确定了后者人群的保护性 Ab 水平为 7.5μg/ml。接受 BNT162b2 或 mRNA-1273 疫苗(PtV)一次接种的个体(n = 21)的血浆样本人群,Ab 浓度的几何平均值显著低于 PV 人群(p < 0.03)。本研究结果对未来疫苗开发、保护效力持续时间预测以及对 SARS-CoV-2 感染免疫反应的理解具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0317/11530011/db7b81d3bbed/pone.0311777.g001.jpg

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