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接种灭活新冠病毒疫苗个体中的初始B细胞和记忆B细胞BCR库

Naive and Memory B Cell BCR Repertoires in Individuals Immunized with an Inactivated SARS-CoV-2 Vaccine.

作者信息

França Renato Kaylan Alves de Oliveira, Barros Pedro Henrique Aragão, Silva Jacyelle Medeiros, Fontinele Hitallo Guilherme Costa, Maranhão Andrea Queiroz, Brigido Marcelo de Macedo

机构信息

Department of Cellular Biology, Institute of Biological Science, University of Brasília, Brasilia 70910-900, DF, Brazil.

Molecular Pathology Post-Graduation Program, University of Brasília, Brasilia 70910-900, DF, Brazil.

出版信息

Vaccines (Basel). 2025 Apr 8;13(4):393. doi: 10.3390/vaccines13040393.

Abstract

BACKGROUND

The COVID-19 pandemic has spurred a global race for a preventive vaccine, with a few becoming available just one year after describing this novel coronavirus disease. Among these are inactivated virus vaccines like CoronaVac (Sinovac Biotech), which are used in several countries to reduce the pandemic's effects. However, its use was associated with low protection, particularly against novel virus variants that quickly appeared in the following months. Vaccines play a crucial role in activating the immune system to combat infections, with Memory B-cells being a key part of this mechanism, eliciting protective neutralizing antibodies. This work focused on studying B-cell memory repertoire after two consecutive doses of CoronaVac.

METHODOLOGY

Memory B-cells were isolated from five CoronaVac vaccinated and five pre-pandemic individuals and subsequently stimulated in vitro before high-throughput Illumina sequencing of the Heavy Chain Variable repertoire.

RESULTS

We observed a shift in the VH repertoire with increased HCDR3 length and enrichment of IGVH 3-23, 3-30, 3-7, 3-72, and 3-74 for IgA BCRs and IGHV 4-39 and 4-59 for IgG BCRs. A high expansion of IgA-specific clonal populations was observed in vaccinated individuals relative to pre-pandemic controls, accompanied by shared IgA variable heavy chain (VH) sequences among memory B cells across different vaccine recipients of IgA clones was also observed in vaccinated individuals compared to pre-pandemic controls, with several IgA VH sharing between memory B cells from different vaccines. Moreover, a high convergence was observed among vaccinees and SARS-CoV-2 neutralizing antibody sequences found in the CoV-abDab database.

CONCLUSION

These data show the ability of CoronaVac to elicit antibodies with characteristics similar to those previously identified as neutralizing antibodies, supporting its protective efficacy. Furthermore, this analysis of the immunological repertoire in the context of viral infections reinforces the importance of immunization in generating convergent antibodies for the antiviral response.

摘要

背景

新冠疫情引发了全球范围内预防疫苗的研发竞赛,在描述这种新型冠状病毒疾病仅一年后,就有几种疫苗可供使用。其中包括科兴生物的克尔来福等灭活病毒疫苗,这些疫苗在多个国家被用于减轻疫情的影响。然而,其使用效果的保护力较低,尤其是对随后几个月迅速出现的新型病毒变种。疫苗在激活免疫系统以对抗感染方面发挥着关键作用,记忆B细胞是这一机制的关键部分,可产生保护性中和抗体。这项研究聚焦于连续接种两剂克尔来福后B细胞记忆库的研究。

方法

从5名接种克尔来福的个体和5名疫情前个体中分离出记忆B细胞,随后在体外进行刺激,然后对重链可变区进行高通量Illumina测序。

结果

我们观察到VH库发生了变化,HCDR3长度增加,IgA BCRs的IGVH 3-23、3-30、3-7、3-72和3-74以及IgG BCRs的IGHV 4-39和4-59富集。与疫情前的对照组相比,接种疫苗的个体中观察到IgA特异性克隆群体的高度扩增,同时在不同疫苗接种者的记忆B细胞中也观察到共享的IgA可变重链(VH)序列。此外,在疫苗接种者与Cov-abDab数据库中发现的SARS-CoV-2中和抗体序列之间观察到高度趋同。

结论

这些数据表明克尔来福能够诱导产生具有与先前鉴定为中和抗体相似特征的抗体,支持其保护效力。此外,这种在病毒感染背景下对免疫库的分析强化了免疫接种在产生抗病毒反应趋同抗体方面的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5b3/12031002/ec8dfa9d4f2d/vaccines-13-00393-g001.jpg

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