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CD21+B细胞频率升高是常见可变免疫缺陷患者对辉瑞-生物科技公司的BNT162b2 mRNA新冠疫苗免疫反应不佳的一个标志。

Elevated CD21 B Cell Frequency Is a Marker of Poor Immunity to Pfizer-BioNTech BNT162b2 mRNA Vaccine Against SARS-CoV-2 in Patients with Common Variable Immunodeficiency.

作者信息

Bergman Peter, Wullimann David, Gao Yu, Wahren Borgström Emilie, Norlin Anna-Carin, Lind Enoksson Sara, Aleman Soo, Ljunggren Hans-Gustaf, Buggert Marcus, Smith C I Edvard

机构信息

Department of Infectious Diseases, Immunodeficiency Unit, Karolinska University Hospital, Stockholm, Sweden.

Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.

出版信息

J Clin Immunol. 2022 May;42(4):716-727. doi: 10.1007/s10875-022-01244-2. Epub 2022 Mar 15.

DOI:10.1007/s10875-022-01244-2
PMID:35290571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8922070/
Abstract

PURPOSE

Limited data is available on the effect of COVID-19 vaccination in immunocompromised individuals. Here, we provide the results from vaccinating a single-center cohort of patients with common variable immunodeficiency (CVID).

METHODS

In a prospective, open-label clinical trial, 50 patients with CVID and 90 age-matched healthy controls (HC) were analyzed for SARS-CoV-2 spike antibody (Ab) production after one or two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Additionally, in selected patients, SARS-CoV-2 spike-specific T-cells were assessed.

RESULTS

A potent vaccine-induced anti-spike-specific IgG Ab response was observed in all the HC. In contrast, only 68.3% of the CVID patients seroconverted, with median titers of specific Ab being 83-fold lower than in HC. In fact, only 4/46 patients (8.6%) of patients who were seronegative at baseline reached the threshold for an optimal response (250 U/mL). Using the EUROclass definition, patients with either a reduced proportion, but not absolute counts, of switched memory B-cells or having an increased frequency of CD21 B-cells generally generated poor vaccine responses. Overall, CVID-patients had reduced spike-specific IFN-γ positive CD4 T cell responses 2 weeks after the second dose, compared to HC. The total CD4 and CD4 central memory cell counts correlated with humoral immunity to the vaccine.

CONCLUSIONS

CVID patients with low frequency of switched memory B-cells or an increased frequency of CD21 B-cells according to the EUROclass definition demonstrated poor responses to Pfizer-BioNTech BNT162b2 mRNA vaccination. Cellular immune responses were significantly affected, affirming that the defect in CVID is not limited to humoral immunity.

摘要

目的

关于新型冠状病毒肺炎(COVID-19)疫苗接种对免疫功能低下个体的影响,现有数据有限。在此,我们提供了对一组单中心常见变异免疫缺陷(CVID)患者进行疫苗接种的结果。

方法

在一项前瞻性、开放标签的临床试验中,分析了50例CVID患者和90例年龄匹配的健康对照(HC)在接种一剂或两剂辉瑞 - 生物科技公司的BNT162b2 mRNA疫苗后,针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突抗体(Ab)的产生情况。此外,还对部分选定患者的SARS-CoV-2刺突特异性T细胞进行了评估。

结果

在所有HC中均观察到了强效的疫苗诱导的抗刺突特异性IgG Ab反应。相比之下,只有68.3%的CVID患者发生血清转化,特异性Ab的中位滴度比HC低83倍。实际上,基线时血清学阴性的患者中只有4/46例(8.6%)达到了最佳反应阈值(250 U/mL)。根据欧洲分类定义,转换记忆B细胞比例降低但不是绝对计数降低,或CD21 B细胞频率增加的患者,通常产生较差的疫苗反应。总体而言,与HC相比,CVID患者在第二剂疫苗接种后2周时,刺突特异性干扰素-γ阳性CD4 T细胞反应降低。总CD4和CD4中央记忆细胞计数与疫苗的体液免疫相关。

结论

根据欧洲分类定义,转换记忆B细胞频率低或CD21 B细胞频率增加的CVID患者,对辉瑞 - 生物科技公司的BNT162b2 mRNA疫苗接种反应较差。细胞免疫反应受到显著影响,证实CVID中的缺陷不仅限于体液免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/994d58ee6929/10875_2022_1244_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/d41785388ddd/10875_2022_1244_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/476e815342b9/10875_2022_1244_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/104201e7f962/10875_2022_1244_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/994d58ee6929/10875_2022_1244_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/d41785388ddd/10875_2022_1244_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/476e815342b9/10875_2022_1244_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/104201e7f962/10875_2022_1244_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b70/9166860/994d58ee6929/10875_2022_1244_Fig4_HTML.jpg

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