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Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2- Recovered Dialysis Patients
Clinical Journal of the American Society of Nephrology ( IF 8.5 ) Pub Date : 2022-07-01 , DOI: 10.2215/cjn.00830122
Philippe Attias 1 , Imane Azzaoui 2, 3 , Khalil El Karoui 4, 5 , Andréa de La Selle 6 , Aurélien Sokal 2, 3 , Pascal Chappert 6, 7 , Philippe Grimbert 4, 5 , Ignacio Fernandez 7 , Magali Bouvier 8, 9 , Chloé Samson 5 , Djamal Dahmane 4 , Philippe Rieu 1 , Patrice Nizard 10 , Slim Fourati 8, 9 , Hamza Sakhi 4, 5 , Matthieu Mahévas 2, 3, 6 ,
Affiliation  

Background and objectives

After two doses of mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients on dialysis show a defective humoral response, but a third dose could increase anti–SARS-CoV-2 spike IgG titers. Responses could be different in virus-naive and SARS-CoV-2–recovered patients on dialysis. However, characterization of memory B cell response after three doses is lacking.

Design, setting, participants, & measurements

We evaluated the dynamics of antireceptor binding domain IgG titers and antireceptor binding domain memory B cells until 6 months after two and three doses (administered within 6 months after the second dose) of mRNA vaccine in SARS-CoV-2–recovered and virus-naive dialysis populations. Results were analyzed by ordinary one-way ANOVA, the Kruskal–Wallis test, or the Wilcoxon matched-pairs test as appropriate.

Results

In total, 108 individuals (59 patients on dialysis and 49 controls) were included. In virus-naive patients on dialysis, antireceptor binding domain IgG response was quantitatively lower after two doses compared with healthy controls, but IgG titers increased by three-fold after three doses (P=0.008). In SARS-CoV-2–recovered patients on dialysis, antireceptor binding domain IgG titers after two doses were significantly higher compared with virus-naive patients on dialysis but did not significantly increase after a third dose. Regarding memory B cell response, we detected receptor binding domain–specific memory B cells at similar proportions in virus-naive patients on dialysis and vaccinated controls after two doses. Moreover, a strong receptor binding domain–specific memory B cell expansion was observed after the third dose in virus-naive patients on dialysis (5.5-fold; P<0.001). However, in SARS-CoV-2–recovered patients on dialysis, antireceptor binding domain memory B cells remained unchanged after the third dose.

Conclusions

The third dose of mRNA vaccine given within 6 months after the second dose boosts serologic and memory response in virus-naive patients but not in SARS-CoV-2–recovered patients on dialysis.

Clinical Trial registry name and registration number:

COVID-19: SARS-CoV-2 Specific Memory B and T-CD4+ Cells (MEMO-COV2), NCT04402892



中文翻译:


未经病毒治疗的透析患者与 SARS-CoV-2 康复的透析患者在注射第三剂 mRNA 疫苗后的免疫反应存在差异



背景和目标


在注射两剂针对​​严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的 mRNA 疫苗后,透析患者表现出体液反应缺陷,但第三剂可能会增加抗 SARS-CoV-2 尖峰 IgG 滴度。未经病毒感染的患者和 SARS-CoV-2 康复的透析患者的反应可能不同。然而,缺乏三个剂量后记忆 B 细胞反应的表征。


设计、设置、参与者和测量


我们评估了 SARS-CoV-2 恢复且未感染病毒的 mRNA 疫苗接种两剂和三剂(第二剂后 6 个月内注射)后 6 个月内的抗受体结合域 IgG 滴度和抗受体结合域记忆 B 细胞的动态透析人群。根据情况,通过普通单向方差分析、Kruskal-Wallis 检验或 Wilcoxon 配对检验对结果进行分析。

 结果


总共包括 108 人(59 名透析患者和 49 名对照者)。在未接触过病毒的透析患者中​​,与健康对照相比,两次给药后抗受体结合域 IgG 反应在数量上较低,但三次给药后 IgG 滴度增加了三倍( P = 0.008)。在 SARS-CoV-2 康复的透析患者中​​,两次给药后抗受体结合域 IgG 滴度显着高于未接触病毒的透析患者,但第三次给药后并没有显着增加。关于记忆 B 细胞反应,我们在未接触病毒的透析患者和接种两次疫苗后的对照组中检测到受体结合域特异性记忆 B 细胞比例相似。此外,在未接触过病毒的透析患者中​​,第三次注射后观察到受体结合域特异性记忆 B 细胞的强烈扩增(5.5 倍; P <0.001)。然而,在 SARS-CoV-2 透析康复患者中,第三次给药后,抗受体结合域记忆 B 细胞保持不变。

 结论


在第二剂疫苗接种后 6 个月内注射第三剂 mRNA 疫苗可以增强未接触过病毒的患者的血清学和记忆反应,但不能增强 SARS-CoV-2 透析康复患者的血清学反应和记忆反应。


临床试验注册名称和注册号:


COVID-19:SARS-CoV-2 特异性记忆 B 和 T-CD4+ 细胞 (MEMO-COV2),NCT04402892

更新日期:2022-07-01
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