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心脏移植受者接种第三剂 BNT162B2 疫苗后 6 个月内细胞和体液反应的动力学——对奥密克戎变异株的影响。

Kinetics of cellular and humoral responses to third BNT162B2 COVID-19 vaccine over six months in heart transplant recipients - implications for the omicron variant.

机构信息

Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.

Sackler Faculty of Medicine, Tel Aviv University, Israel; General Management, Sheba Medical Center, Israel.

出版信息

J Heart Lung Transplant. 2022 Oct;41(10):1417-1425. doi: 10.1016/j.healun.2022.05.014. Epub 2022 May 24.

DOI:10.1016/j.healun.2022.05.014
PMID:35710484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9128305/
Abstract

BACKGROUND

The durability of the immune response following the 3-dose BNT162b2 vaccination is unknown. The complexity of the situation is enhanced by the threat that highly transmissible variants may further accelerate the decline in the protection afforded by mRNA vaccines.

METHODS

One hundred and three 3-dose-vaccinated heart transplant recipients were longitudinally assessed for the kinetics of variant-specific neutralization (Cohort 1, n = 60) and SARS-CoV-2-specific-T-cell response (Cohort 2, n = 54) over 6 months. Neutralization and T-cell responses were compared between paired samples at 2 time points, using the Kruskal-Wallis test followed by Dunn's multiple comparison test for continuous variables and McNemar's test for dichotomous variables. The Bonferroni method of p values adjustment for multiple comparison was applied.

RESULTS

The third dose induced high neutralization of the wild-type virus and delta variant (geometric mean titer [GMT], 137.2 [95% CI, 84.8-221.9] and 80.6, [95% CI, 49.3-132.0], respectively), and to a lesser degree of the omicron variant (GMT, 10.3 [95% CI, 5.9-17.9]). At 6 months, serum neutralizing activity declined but was still high for the wild-type virus and for the delta variant (GMTs 38.1 [95% CI, 21.2-69.4], p = 0.011; and 28.9 [95% CI, 16.6-52.3], p = 0.022, respectively), but not for the omicron variant (GMT 5.9 [95% CI, 3.4-9.8], p = 0.463). The percentages of neutralizing sera against the wild-type virus, delta and omicron variants increased from 70%, 65%, and 38%, before the third dose, to 93% (p < 0.001), 88% (p < 0.001), and 48% (p = 0.021) at 3 weeks after, respectively; and remained high through the 6 months for the wild-type (80%, p = 0.06) and delta (77%, p = 0.102). The third dose induced the development of a sustained SARS-CoV-2-specific-T-cell population, which persisted through 6 months.

CONCLUSIONS

The third BNT162b2 dose elicited a durable SARS-CoV-2-specific T-cell response and induced effective and durable neutralization of the wild-type virus and the delta variant, and to a lesser degree of the omicron variant.

摘要

背景

目前尚不清楚接种 3 剂 BNT162b2 疫苗后的免疫反应持续时间。高传染性变异株可能会进一步加速 mRNA 疫苗提供的保护作用下降,这使得情况更加复杂。

方法

103 例接受 3 剂疫苗接种的心移植受者在 6 个月内进行了变异特异性中和(队列 1,n=60)和 SARS-CoV-2 特异性 T 细胞反应(队列 2,n=54)的纵向评估。使用 Kruskal-Wallis 检验 followed by Dunn's 多重比较检验对连续变量进行比较,使用 McNemar 检验对二项变量进行比较。应用 Bonferroni 方法对多个比较的 p 值进行调整。

结果

第 3 剂诱导了针对野生型病毒和 delta 变异株的高中和抗体(几何平均滴度 [GMT],分别为 137.2 [95% CI,84.8-221.9]和 80.6 [95% CI,49.3-132.0]),以及对 omicron 变异株的中和抗体的中和能力较低(GMT,10.3 [95% CI,5.9-17.9])。6 个月时,血清中和活性下降,但对野生型病毒和 delta 变异株仍保持较高水平(GMTs 分别为 38.1 [95% CI,21.2-69.4],p=0.011;和 28.9 [95% CI,16.6-52.3],p=0.022),但对 omicron 变异株(GMT 5.9 [95% CI,3.4-9.8],p=0.463)没有效果。中和针对野生型病毒、delta 和 omicron 变异株的血清百分比从第 3 剂前的 70%、65%和 38%增加到第 3 剂后 3 周的 93%(p<0.001)、88%(p<0.001)和 48%(p=0.021);并且在 6 个月时,针对野生型(80%,p=0.06)和 delta(77%,p=0.102)的中和水平仍保持较高水平。第 3 剂诱导了 SARS-CoV-2 特异性 T 细胞的持续产生,这种反应在 6 个月内仍持续存在。

结论

第 3 剂 BNT162b2 疫苗诱导了 SARS-CoV-2 特异性 T 细胞的持久反应,并诱导了针对野生型病毒和 delta 变异株的有效且持久的中和作用,对 omicron 变异株的中和作用则较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/7e5e734aa573/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/38d7c356c889/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/5c2c0e11c0f0/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/bcf5d2e4b54f/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/7e5e734aa573/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/38d7c356c889/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/5c2c0e11c0f0/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/bcf5d2e4b54f/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/9128305/7e5e734aa573/gr4_lrg.jpg

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