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Ad5-nCoV 增强型疫苗和再感染诱导的记忆 T/B 细胞反应及体液免疫对 SARS-CoV-2 的作用:基于两项前瞻性队列研究。

Ad5-nCoV boosted vaccine and reinfection-induced memory T/B cell responses and humoral immunity to SARS-CoV-2: based on two prospective cohorts.

机构信息

Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, People's Republic of China.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China.

出版信息

Emerg Microbes Infect. 2024 Dec;13(1):2412619. doi: 10.1080/22221751.2024.2412619. Epub 2024 Oct 28.

DOI:10.1080/22221751.2024.2412619
PMID:39360715
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11529888/
Abstract

Here, we regularly followed two SARS-CoV-2 infected cohorts to investigate the combined effects of neutralizing antibodies (NAbs) and B and T cell profiles during the convalescent period. Ten infected participants in December 2022 were selected to assess the effects of an inhaled adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) booster on B cells and humoral immunity in the first cohort. To evaluate T cell responses, eight primary and 20 reinfection participants were included in the second cohort. Blood samples from all 38 participants were collected at 1-, 2-, and 6-months post-infection. In the first cohort, eighteen monoclonal antibodies (mAbs) with neutralizing activity from memory B cells (MBC) against SARS-CoV-2 mutants were obtained by high throughput single-B-cell cloning method, which lasted from 1- month to 6- month post infection. The overall number of mAbs from MBC in the boosted immunization group was higher than that in the nonboosted immunization group at 2-, and 6-months post-infection. In the second cohort, circulating T follicular helper cells (cTfh) and AIM CD4 T cells increased over time in the reinfection group ( < 0.05). In both cohorts, serum NAb titers showed significant immune escape, while cTfh and AIM CD4 T cells in the second cohort essentially showed no immune escape to new strains (including XBB, EG.5). AIM CD4 T cells against BA.5 and EG.5 were strongly negatively correlated with the time to viral clearance in the reinfected group at 6-months post-infection. We comprehensively assessed the ability of the SARS-CoV-2 boosted immunization and reinfection-induced generation of T/B cell immune memories in preventing reinfection.

摘要

在这里,我们定期随访了两例 SARS-CoV-2 感染队列,以研究恢复期中和抗体(NAb)和 B 细胞与 T 细胞特征的综合影响。选择 2022 年 12 月的 10 例感染参与者评估吸入型腺病毒 5 型载体 COVID-19 疫苗(Ad5-nCoV)加强剂对第一队列 B 细胞和体液免疫的影响。为了评估 T 细胞反应,第二队列纳入了 8 例初次感染和 20 例再感染参与者。所有 38 名参与者的血液样本均在感染后 1、2 和 6 个月采集。在第一队列中,通过高通量单细胞克隆方法从记忆 B 细胞(MBC)中获得了针对 SARS-CoV-2 突变体具有中和活性的 18 种单克隆抗体(mAb),持续时间从感染后 1 个月到 6 个月。在感染后 2 个月和 6 个月,加强免疫组的 MBC 产生的 mAb 总数高于非加强免疫组。在第二队列中,再感染组的循环滤泡辅助 T 细胞(cTfh)和 AIM-CD4-T 细胞随时间推移而增加(<0.05)。在两个队列中,血清 NAb 滴度均显示出显著的免疫逃逸,而第二队列中的 cTfh 和 AIM-CD4-T 细胞对新毒株(包括 XBB、EG.5)基本上没有免疫逃逸。再感染组感染后 6 个月时,AIM-CD4-T 细胞对 BA.5 和 EG.5 的反应与病毒清除时间呈强烈负相关。我们全面评估了 SARS-CoV-2 加强免疫和再感染诱导的 T/B 细胞免疫记忆产生在预防再感染方面的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/21b111801d3f/TEMI_A_2412619_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/19f0b650d56d/TEMI_A_2412619_F0001_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/3ab0b67ab180/TEMI_A_2412619_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/2e8ed537e048/TEMI_A_2412619_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/da460ae06274/TEMI_A_2412619_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/cf8863140388/TEMI_A_2412619_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/21b111801d3f/TEMI_A_2412619_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/19f0b650d56d/TEMI_A_2412619_F0001_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/3ab0b67ab180/TEMI_A_2412619_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/2e8ed537e048/TEMI_A_2412619_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/da460ae06274/TEMI_A_2412619_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/cf8863140388/TEMI_A_2412619_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/11529888/21b111801d3f/TEMI_A_2412619_F0006_OC.jpg

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