Elevated CD21low 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

CD21low B 细胞频率升高是患有常见变异性免疫缺陷症的患者对辉瑞-BioNTech BNT162b2 mRNA 疫苗免疫力较差的标志

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

Conclusions

CVID patients with low frequency of switched memory B-cells or an increased frequency of CD21low 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.

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.

Purpose

Limited data is available on the effect of COVID-19 vaccination in immunocompromised individuals. Here, we provide the

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 CD21low 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 CD21low 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.

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