Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals.
Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals.
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DOI：
10.1128/spectrum.01315-22
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发表时间：
2022-10-26
影响因子：
3.7
通讯作者：
Goldfarb, David M.
中科院分区：
文献类型：
--
作者：
Grunau, Brian;Prusinkiewicz, Martin;Asamoah-Boaheng, Michael;Golding, Liam;Lavoie, Pascal M.;Petric, Martin;Levett, Paul N.;Haig, Scott;Barakauskas, Vilte;Karim, Mohammad Ehsanul;Jassem, Agatha N.;Drews, Steven J.;Sediqi, Sadaf;Goldfarb, David M.
SARS-CoV-2抗刺突抗体浓度和血管紧张素转换酶-2（ACE-2）抑制已被用作活病毒中和抗体滴度的替代物;然而，在接种疫苗的个体中的有效性尚不清楚。我们在接种疫苗的参与者中测试了这些指标的相关性，并根据接种疫苗后的持续时间和疫苗给药间隔检查了亚组。我们分析了120份来自两剂mRNA疫苗接种者的样本，这些人之前没有COVID-19。我们计算了野生型病毒中和抗体滴度与以下抗体之间的斯皮尔曼相关系数：抗刺突（总和IgG）、抗受体结合结构域（RBD）和抗N末端结构域（NTD）抗体;以及RBD与ACE-2的结合。我们进行了三次二次分析，通过第一次疫苗接种至采血间隔、第二次疫苗接种至采血间隔和疫苗给药间隔（所有组除以中位数）对样本进行二分，并比较相关系数（Fisher's Z检验）。在120名参与者中，63名（53%）是女性，91名（76%）和29名（24%）分别接受了BNT 162b2和mRNA-1273疫苗。总体而言，活病毒中和与抗加标总抗体（相关系数= 0.80）、抗加标IgG（0.63）、抗RBD IgG（0.62）、抗NTD IgG（0.64）和RBD ACE 2结合（0.65）相关。与短时间组相比，首次接种至采血间隔较长（> 158天）和第二次接种至采血间隔较长（> 71天）的样本显示出更高的相关系数。当比较按短（≤ 39天）与长疫苗给药间隔划分的病例时，仅长组中与RBD-ACE-2结合抑制的相关性较高。在COVID阴性mRNA疫苗接种者中，抗刺突抗体和ACE-2抑制浓度与活病毒中和抗体滴度相关。在疫苗接种后较晚时间采集的样本之间的相关性更强。重要性活病毒中和抗体滴度是公认的免疫指标;然而，检测程序是劳动密集型的。COVID-19抗体和血管紧张素转换酶-2（ACE-2）水平已被用作活病毒中和抗体滴度的替代物;然而，在接种疫苗的个体中的有效性尚不清楚。使用来自120名先前没有COVID-19的两剂mRNA疫苗接种者的样本，我们发现活病毒中和与COVID-19抗体和ACE2结合水平相关。当根据疫苗接种和样本血液采集之间的时间间隔对样本进行分组时，与早期采集的样本相比，首次疫苗接种后158天以上和第二次疫苗接种后71天以上采集的样本显示活病毒中和滴度与抗体和ACE 2水平之间的相关性更强。
SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher’s Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.
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影响因子：
8
作者：
Abe, Kento T.;Li, Zhijie;Gingras, Anne-Claude
通讯作者：
Gingras, Anne-Claude
DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
DOI：
10.1016/s1473-3099(20)30634-4
发表时间：
2020-12
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
National SARS-CoV-2 Serology Assay Evaluation Group
通讯作者：
National SARS-CoV-2 Serology Assay Evaluation Group
影响因子：
12.7
作者：
Dolscheid-Pommerich R;Bartok E;Renn M;Kümmerer BM;Schulte B;Schmithausen RM;Stoffel-Wagner B;Streeck H;Saschenbrecker S;Steinhagen K;Hartmann G
通讯作者：
Hartmann G
影响因子：
3.7
作者：
Diedenhofen B;Musch J
通讯作者：
Musch J