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SARS-CoV-2 特异性 CD4 T 细胞与中和抗体的长期持久性相关。

SARS-CoV-2-specific CD4 T cells are associated with long-term persistence of neutralizing antibodies.

机构信息

State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

The Second People's Hospital of Changde, Hunan, China.

出版信息

Signal Transduct Target Ther. 2022 Apr 23;7(1):132. doi: 10.1038/s41392-022-00978-0.

DOI:10.1038/s41392-022-00978-0
PMID:35461307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9034077/
Abstract

Understanding the decay and maintenance of long-term SARS-CoV-2 neutralizing antibodies in infected or vaccinated people and how vaccines protect against other SARS-CoV-2 variants is critical for assessing public vaccination plans. Here, we measured different plasm antibody levels 2 and 12 months after disease onset, including anti-RBD, anti-N, total neutralizing antibodies, and two neutralizing-antibody clusters. We found that total neutralizing antibodies declined more slowly than total anti-RBD and anti-N IgG, and the two neutralizing-antibody clusters decayed even more slowly than total neutralizing antibodies. Interestingly, the level of neutralizing antibodies at 12 months after disease onset was significantly lower than that at 2 months but more broadly neutralized SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Lambda (C.37). Significant immune escape by the Omicron variant (B.1.1.529) was also observed 2 months post-recovery. Furthermore, we revealed that a high percentage of virus-specific CD4 T cells and cTfh1 were associated with a slower decline in humoral immunity, accompanied by higher levels of CXCR3 ligands such as CXCL9 and CXCL10, higher frequency of cTfh1, and lower levels of cTfh2 and cTfh17. Our data highlight the importance of coordinating T-cell and humoral immunity to achieve long-term protective immunity.

摘要

了解感染或接种疫苗的人群中 SARS-CoV-2 中和抗体的衰减和维持情况,以及疫苗如何预防其他 SARS-CoV-2 变体,对于评估公众接种计划至关重要。在这里,我们测量了发病后 2 个月和 12 个月时的不同浆细胞抗体水平,包括抗 RBD、抗 N、总中和抗体和两个中和抗体簇。我们发现,总中和抗体的下降速度比总抗 RBD 和抗 N IgG 慢,而两个中和抗体簇的衰减速度甚至更慢。有趣的是,发病后 12 个月时的中和抗体水平明显低于发病后 2 个月时,但更广泛地中和了 SARS-CoV-2 变体,包括 Alpha(B.1.1.7)、Beta(B.1.351)、Gamma(P.1)、Delta(B.1.617.2)和 Lambda(C.37)。在恢复期后 2 个月还观察到奥密克戎变异株(B.1.1.529)的显著免疫逃逸。此外,我们揭示了高比例的病毒特异性 CD4 T 细胞和 cTfh1 与体液免疫的下降速度较慢有关,伴随着更高水平的 CXCR3 配体,如 CXCL9 和 CXCL10,更高频率的 cTfh1,以及更低水平的 cTfh2 和 cTfh17。我们的数据强调了协调 T 细胞和体液免疫以实现长期保护免疫的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb01/9035185/c30db6e60f58/41392_2022_978_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb01/9035185/c30db6e60f58/41392_2022_978_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb01/9035185/7b34bbe18e0c/41392_2022_978_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb01/9035185/e1d364c7c3dc/41392_2022_978_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb01/9035185/8fb3122548fc/41392_2022_978_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb01/9035185/6158089fef72/41392_2022_978_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb01/9035185/c30db6e60f58/41392_2022_978_Fig5_HTML.jpg

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