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Clinical Trial
. 2022 Jul;17(7):1008-1016.
doi: 10.2215/CJN.00830122. Epub 2022 Jun 28.

Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2- Recovered Dialysis Patients

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 ; Mondor NephroCov Study Group
Collaborators, Affiliations
Clinical Trial

Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2- Recovered Dialysis Patients

Philippe Attias et al. Clin J Am Soc Nephrol. 2022 Jul.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; dialysis; immunology; mRNA vaccine; memory B cells.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Humoral and memory B cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) in virus-naive and SARS-CoV-2–recovered patients on dialysis after mRNA vaccination. (A) Antibody response. Median ± interquartile range (IQR) anti−SARS-CoV-2 RBD serum IgG titers measured by ELISA in virus-naive (left panel; white dots) and SARS-CoV-2–recovered individuals (right panel; mild coronavirus disease 2019 [COVID-19]: orange dots; severe COVID-19: red dots). White bars represent virus-naive (n=23) or SARS-CoV-2–recovered (n=26) healthy controls 1–2 months after two doses or one dose of mRNA vaccine, respectively (#). Light blue bars represent virus-naive (n=20) and SARS-CoV-2–recovered (n=20) patients on dialysis 1–2 months after a second dose of mRNA vaccine. Dark blue bars represent virus-naive (n=25) and SARS-CoV-2–recovered (n=13) patients on dialysis 1–2 months (median of 50 days) after a third dose of mRNA vaccine. (B) Antibody response. Longitudinal evolution of anti–SARS-CoV-2 RBD IgG titers after a third dose of mRNA vaccine in virus-naive (n=13) and SARS-CoV-2–recovered (n=7) patients on dialysis (median time from second dose to third dose: 153.5 [IQR, 145–155] days) and 6 months after a second dose in SARS-CoV-2–recovered (n=6) patients on dialysis. (C) Memory B cell response. Median ± IQR frequencies of SARS-CoV-2 RBD-specific cells in live CD19+IgD−CD27+CD38int/− memory B cells by flow cytometry in virus-naive and SARS-CoV-2–recovered individuals. (D) Memory B cell response. Frequencies of SARS-CoV-2 RBD-specific memory B cells after a third dose of mRNA vaccine in virus-naive (n=14) and SARS-CoV-2–recovered (n=7) patients on dialysis (median time from second dose to third dose: 153.5 [IQR, 145–155] days) and 6 months after a second dose in SARS-CoV-2–recovered (n=5) patients on dialysis. Kruskal–Wallis test with multiple comparisons between groups for (A) and (C) and Wilcoxon matched-pairs signed rank test for (B) and (D). Bars indicate median ± IQR. Values equal to zero were converted to 0.01 for logarithmic scale. **P<0.01; ***P<0.001; ****P<0.0001. 6M, 6 months; ns, nonsignificant; S, spike; A.U, arbitrary unit.
Figure 2.
Figure 2.
Characterization of the anti-RBD B cell response. (A) Median ± IQR of frequencies of SARS-CoV-2 RBD-specific cells in live CD19+IgD−CD27−CD38int/− DN B cells by flow cytometry in virus-naive (left panel; white dots) and SARS-CoV-2–recovered individuals (right panel; mild COVID-19: orange dots; severe COVID-19: red dots). White bars represent virus-naive (n=23) or SARS-CoV-2–recovered (n=23) healthy controls 1–2 months after two doses or one dose of mRNA vaccine, respectively (#). Light blue bars represent virus-naive (n=19) and SARS-CoV-2–recovered (n=17) patients on dialysis 1–2 months after a second dose of mRNA vaccine. Dark blue bars represent virus-naive (n=23) and SARS-CoV-2–recovered (n=13) patients on dialysis 1–2 months (median 50 days) after a third dose of mRNA vaccine. (B) Median ± IQR of frequencies of SARS-CoV-2 RBD-specific cells displaying a DN2 (CD19+CD27−IgD−CD11c+CD21−) or a DN1 (CD19+CD27−IgD−CD11c−CD21+) phenotype in virus-naive (n=9) and SARS-CoV-2–recovered (=18) healthy controls 1–2 months after two doses or one dose of mRNA vaccine, respectively; in virus-naive (n=9) and SARS-CoV-2–recovered (n=15) patients on dialysis 1–2 months after a second dose of mRNA vaccine; and in virus-naive (n=17) and SARS-CoV-2–recovered (n=9) patients on dialysis 1–2 months (median of 50 days) after a third dose of mRNA vaccine. We performed repeated measures mixed effects model analysis with multiple comparisons between time points for dialysis groups and Kruskal–Wallis with multiple comparisons between donor groups inside each time point and between vaccinated controls groups. Bars indicate median ± IQR. Values equal to zero were converted to 0.01 for logarithmic scale. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. DN, double negative; S, spike; AU, arbitrary unit.
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