Persistently reduced humoral and sustained cellular immune response from first to third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients.

Persistently reduced humoral and sustained cellular immune response from first to third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients.
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DOI:
10.1016/j.msard.2022.103729
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发表时间:
2022-04
影响因子:
4
通讯作者:
Sejbaek T
Sejbaek T
中科院分区:
医学3区
文献类型:
--
作者:
Bajwa HM;Novak F;Nilsson AC;Nielsen C;Holm DK;Østergaard K;Witt AH;Byg KE;Johansen IS;Mittl K;Rowles W;Zamvil SS;Bove R;Sabatino JJ;Sejbaek T

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研究多发性硬化症患者在第三次BNT162b2 mRNA SARS-CoV-2疫苗接种后抗cd20治疗的体液和细胞反应。丹麦和美国多发性硬化症中心从第一次到第三次接种疫苗的前瞻性纵向研究设计。所有参与者均接受ocrelizumab治疗。使用SARS-CoV-2 IgG II定量测定法(雅培实验室)评估第三次疫苗接种前后的抗体(Ab)水平。B淋巴细胞和t淋巴细胞计数采用BD Multitest™6色TBNK试剂。通过刺突肽池(JPT peptide Technologies)刺激PBMC来测量刺突特异性t细胞反应。第一次、第二次和第三次接种后血清阳性率分别为14.0%、37.7%和33.3%。第二次接种后的中位抗体水平为74.2 BAU/mL(范围:8.5-2427),第三次接种前和后分别为43.7 BAU/mL(范围:7.8-366.1)和31.3 BAU/mL(范围:7.9-507.0)。在第二次和第三次接种疫苗后,其水平无差异(p = 0.1475)。在第三次疫苗接种前,血清阳性率下降到25.0%,相对降低33.3% (p = 0.0020)。第二次接种和第三次接种后CD4+和CD8+ t细胞尖峰反应频率(分别为0.65±0.08%和0.95±0.20%)和CD8+ t细胞尖峰反应频率(分别为0.99±0.22%和1.3±0.34%)无显著差异。在这个纵向队列中,我们发现接种第三次SARS-CoV-2 mRNA疫苗后,体液或细胞反应没有显著增加。这些发现表明,临床策略需要包括在重复接种疫苗之前允许B细胞重构和/或提供暴露前预防性单克隆抗体。
To examine humoral and cellular response in multiple sclerosis patients on anti-CD20 therapy after third BNT162b2 mRNA SARS-CoV-2 vaccination. A prospective longitudinal study design from first throughout third vaccination in Danish and American MS centers. All participants were treated with ocrelizumab. Antibody (Ab) levels were assessed before and after third vaccination using SARS-CoV-2 IgG II Quant assay (Abbott Laboratories). B- and T-lymphocytes enumeration was done with BD Multitest™6-color TBNK reagent. Spike-specific T-cell responses were measured through PBMC stimulation with spike peptide pools (JPT Peptide Technologies). We found that 14.0%, 37.7%, and 33.3% were seropositive after first, second and third vaccination. The median Ab-levels were 74.2 BAU/mL (range: 8.5–2427) after second vaccination, as well as 43.7 BAU/ml (range: 7.8–366.1) and 31.3 BAU/mL (range: 7.9–507.0) before and after third vaccination, respectively. No difference was found in levels after second and third vaccination (p = 0.1475). Seropositivity dropped to 25.0% of participants before the third vaccination, a relative reduction of 33.3% (p = 0.0020). No difference was found between frequencies of spike reactive CD4+and CD8+ T-cells after second (0.65 ± 0.08% and 0.95 ± 0.20%, respectively) and third vaccination (0.99 ± 0.22% and 1.3 ± 0.34%, respectively). In this longitudinal cohort we found no significant increased humoral or cellular response with administration of a third SARS-CoV-2 mRNA vaccination. These findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.
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发表时间: 2021-11
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