Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the Study Population
2.2. Antibody and Spike-Specific T-Cell Response in PwMS and HCWs at T1
2.3. Antibody and Spike-Specific T-Cell Response in PwMS and HCWs at T2
2.4. Temporal Evolution of the Antibody Response to COVID-19 Vaccination in Both HCWs and PwMS
2.5. SARS-CoV-2-Spike-Specific T-Cell Response Persists over Time in Both Cohorts
3. Discussion
3.1. Limitations of the Study
3.2. Conclusions
4. Materials and Methods
4.1. Study Population
4.2. Study Procedures
4.3. Anti-SARS-CoV-2 Antibody Testing
4.4. IFN-γ Release Assay (IGRA)
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | PwMS | HCWs | p Value | |
---|---|---|---|---|
N (%) | 121 (55) | 99 (45) | ||
Age median (IQR) | 47 (39–55) | 43 (31–52) | 0.001 * | |
Female N (%) | 85 (70.2) | 72 (72.7) | 0.685 § | |
Origin N (%) | West Europe | 118 (97.5) | 97 (98) | 0.531 § |
East Europe | 2 (1.7) | 1 (1.0) | ||
Asia | 0 (0) | 1 (1.0) | ||
South America | 1 (0.8) | 0 (0) | ||
BMI (kg/mq), median (IQR) | 23.7 (21.2–26.4) | - | ||
MS duration, median (IQR) | 14 (8–22) | - | ||
MS course N (%) | Relapsing-remitting | 110 (90) | - | |
Primary-progressive | 11 (10) | - | ||
EDSS score, median (IQR) | 2 (1–4) | - | ||
Multiple sclerosis treatment N (%) | Ocrelizumab | 34 (28.1) | - | |
Fingolimod | 35 (28.9) | - | ||
Cladribine | 20 (16.5) | - | ||
IFN-β | 32 (26.5) | - | ||
Lymphocytes count N (%) | Available | 105 (86.8) | 0 (0) | |
Lymphocytes count N (%) Median × 103/µL (IQR) | Ocrelizumab | 34 (32.4) 1.62 (1.28–1.89) | - | <0.0001 ** |
Fingolimod | 35 (33.3) 0.65 (0.57–0.91) | - | ||
Cladribine | 19 (18.1) 1.10 (0.87–1.45) | - | ||
IFN-β | 17 (16.2) 1.65 (1.53–2.06) | - | ||
Time between withdrawals, median days (IQR) | T0-T1 | 161 (159–163) | 139 (135–141) | |
T1-T2 | 63 (52–77) | 168 (159–178) | ||
T0-T2 | 218 (210–235) | 305 (298–316) |
Characteristics | p Value | ||||||
---|---|---|---|---|---|---|---|
PwMS | HCWs | Within MS Cohort | PwMS vs. HCWs | ||||
N (%) | 105 (54.1) | 89 (45.9) | |||||
Antibody response | Qualitative response | anti-RBD abs responders N (%) | 69 (65.7) | 89 (100) | <0.0001 § | ||
anti-RBD abs responders within the subgroups N (%) | Ocrelizumab | 6/29 (20.7) | - | <0.0001 § | <0.0001 § | ||
Fingolimod | 18/31 (58.1) | - | <0.0001 § | ||||
Cladribine | 18/18 (100) | - | - | ||||
IFN-β | 27/27 (100) | - | - | ||||
Quantitative response | anti-RBD titers BAU/mL median (IQR) | 32 (2.4–104) | 177 (95.5–262.6) | <0.0001 * | |||
Ocrelizumab | 0.80 (0.15–6.25) | - | <0.0001 # | <0.0001 * | |||
Fingolimod | 7.9 (2.7–39.7) | - | <0.0001 * | ||||
Cladribine | 85.9 (48–137) | - | 0.002 * | ||||
IFN-β | 126.4 (80–184) | - | 0.047 * | ||||
Spike-specific IFN-γ T-cell response | Qualitative response | spike responders N (%) | 63 (60) | 88 (98.9) | <0.0001 § | ||
spike responders within the subgroups N (%) | Ocrelizumab | 28/29 (96.5) | - | <0.0001 § | 0.399 § | ||
Fingolimod | 1/31 (3.2) | - | <0.0001 § | ||||
Cladribine | 11/18 (61.1) | - | <0.0001 § | ||||
IFN-β | 23/27 (85.2) | - | 0.002 § | ||||
Quantitative response | spike IFN-γ levels pg/mL median (IQR) | 39.9 (3.4–142.5) | 218 (93–378) | <0.0001 * | |||
Ocrelizumab | 114 (64–193) | - | <0.0001 # | 0.006 * | |||
Fingolimod | 0.8 (0.1–3.3) | - | <0.0001 * | ||||
Cladribine | 32 (7–139) | - | <0.0001 * | ||||
IFN-β | 79 (33–237) | - | 0.003 * |
PwMS vs. HCWs | ||||||
---|---|---|---|---|---|---|
RBD | T1 | T2 | ||||
IRR | 95%CI | p | IRR | 95%CI | p | |
HCWs | 1.00 | 1.00 | ||||
IFN-β | 1.96 | 0.78–4.91 | 0.149 | 2.92 | 1.32–6.44 | 0.008 |
Cladribine | 1.19 | 0.48–2.92 | 0.708 | 1.67 | 0.59–4.77 | 0.334 |
Fingolimod | 0.32 | 0.14–0.75 | 0.009 | 0.14 | 0.07–0.28 | <0.001 |
Ocrelizumab | 0.05 | 0.02–0.12 | <0.001 | 0.09 | 0.05–0.18 | <0.001 |
Weeks elapsed from the vaccination | 0.82 | 0.68–0.97 | <0.001 | 0.72 | 0.61–0.86 | <0.001 |
Within PwMS cohort | ||||||
RBD | T1 | T2 | ||||
IRR | 95%CI | p | IRR | 95%CI | p | |
IFN-β | 1.00 | 1.00 | ||||
Cladribine | 0.78 | 0.29–2.11 | 0.624 | 0.50 | 0.08–3.20 | 0.465 |
Fingolimod | 0.23 | 0.10–0.53 | 0.001 | 0.04 | 0.01–0.16 | <0.001 |
Ocrelizumab | 0.04 | 0.02–0.12 | <0.001 | 0.03 | 0.01–0.22 | <0.001 |
Treatment duration | 1.02 | 0.95–1.09 | 0.585 | 0.98 | 0.88–1.10 | 0.776 |
EDSS | 0.96 | 0.84–1.09 | 0.488 | 1.08 | 0.84–1.39 | 0.546 |
PwMS vs. HCWs | ||||||
Spike | T1 | T2 | ||||
IRR | 95%CI | p | IRR | 95%CI | p | |
HCWs | 1.00 | 1.00 | ||||
IFN-β | 0.78 | 0.17–3.45 | 0.743 | 0.55 | 0.27–1.12 | 0.098 |
Cladribine | 0.33 | 0.07–1.54 | 0.163 | 0.12 | 0.05–0.30 | <0.001 |
Fingolimod | 0.01 | 0.002–0.04 | <0.001 | 0.003 | 0.002–0.01 | <0.001 |
Ocrelizumab | 0.73 | 0.18–2.96 | 0.662 | 0.48 | 0.24–0.96 | 0.037 |
Weeks elapsed from the vaccination | 0.91 | 0.67–1.25 | 0.586 | |||
Age | 0.97 | 0.96–0.99 | 0.009 | |||
Within PwMS cohort | ||||||
Spike | T1 | T2 | ||||
IRR | 95%CI | p | IRR | 95%CI | p | |
IFN-β | 1.00 | 1.00 | ||||
Cladribine | 0.68 | 0.26–1.75 | 0.421 | 0.23 | 0.08–0.72 | 0.012 |
Fingolimod | 0.02 | 0.01–0.04 | <0.001 | 0.01 | 0.001–0.01 | <0.001 |
Ocrelizumab | 1.13 | 0.49–2.57 | 0.778 | 0.90 | 0.38–2.15 | 0.814 |
Lymphocytes | 1.01 | 0.74–1.38 | 0.939 | 0.92 | 0.61–1.40 | 0.709 |
Characteristics | p Value | ||||||
---|---|---|---|---|---|---|---|
PwMS | HCWs | Within MS Cohort | PwMS vs. HCWs | ||||
N (%) | 82 (68.3) | 38 (31.7) | |||||
Antibody response | Qualitative response | anti-RBD abs responders N (%) | 64 (78) | 38 (100) | 0.0017 § | ||
anti-RBD abs responders within the subgroups N (%) | Ocrelizumab | 5/22 (22.7) | - | <0.0001 § | <0.0001 § | ||
Fingolimod | 29/30 (96.7) | - | 0.257 § | ||||
Cladribine | 10/10 (100) | - | - | ||||
IFN-β | 20/20 (100) | - | - | ||||
Quantitative response | anti-RBD titers BAU/mL median (IQR) | 408 (11.6–4235) | 4516 (3098–5477) | <0.0001 * | |||
Ocrelizumab | 0.55 (0.27–6.27) | - | <0.0001 # | <0.0001 * | |||
Fingolimod | 174 (26–514) | - | <0.0001 * | ||||
Cladribine | 3455 (1300–6060) | - | 0.295 * | ||||
IFN-β | 6060 (3906–9414) | - | 0.023 * | ||||
Spike-specific IFN-γ T-cell response | Qualitative response | spike responders N (%) | 49 (59.7) | 38 (100) | <0.0001 § | ||
spike responders within the subgroups N (%) | Ocrelizumab | 22/22 (100) | - | <0.0001 § | - | ||
Fingolimod | 1/30 (3.3) | - | <0.0001 § | ||||
Cladribine | 8/10 (80) | - | 0.005 § | ||||
IFN-β | 18/20 (90) | - | 0.047 § | ||||
Quantitative response | spike IFN-γ levels pg/mL median (IQR) | 71.9 (1.2–334.5) | 426 (196–792) | <0.0001 * | |||
Ocrelizumab | 352 (230–544) | - | <0.0001 # | 0.364 * | |||
Fingolimod | 0.6 (0.1–2.6) | - | <0.0001 * | ||||
Cladribine | 75 (35–176) | - | <0.0001 * | ||||
IFN-β | 215 (99–728) | - | 0.084 * |
T0 | T1 | T2 | p Value | |||
---|---|---|---|---|---|---|
HCWs | N (%) | 25 (100%) | 25 (100%) | 25 (100%) | ||
Qualitative response | Antibody responders N (%) | 25/25 (100%) | 25/25 (100%) | 25/25 (100%) | - | |
T-cell responders N (%) | 25/25 (100%) | 25/25 (100%) | 25/25 (100%) | - | ||
Quantitative response | anti-RBD titers BAU/mL median (IQR) | 3377 (1647–4839) | 178 (132–271) | 4608 (3040–6408) | <0.0001 # | |
spike IFN-γ levels pg/mL median (IQR) | 262 (118–531) | 196 (66–490) | 525 (234–812) | 0.012 # | ||
PwMS | N (%) | 64 (100%) | 64 (100%) | 64 (100%) | ||
Qualitative response | Antibody responders N (%) | 49/64 (76.6%) | 37/64 (57.8%) | 48/64 (75%) | <0.0001 * | |
T-cell responders N (%) | 35/64 (54.7%) | 33/64 (51.6%) | 37/64 (57.8%) | 0.368 * | ||
Quantitative response | anti-RBD titers BAU/mL median (IQR) | 52.8 (7.8–1165) | 13.2 (1.6–98.6) | 272.5 (6.0–4558) | <0.0001 # | |
spike IFN-γ levels pg/mL median (IQR) | 52.4 (1.7–178) | 20.8 (1.7–171) | 78.6 (1.0–351) | 0.031 # |
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Ruggieri, S.; Aiello, A.; Tortorella, C.; Navarra, A.; Vanini, V.; Meschi, S.; Lapa, D.; Haggiag, S.; Prosperini, L.; Cuzzi, G.; et al. Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose. Int. J. Mol. Sci. 2023, 24, 8525. https://doi.org/10.3390/ijms24108525
Ruggieri S, Aiello A, Tortorella C, Navarra A, Vanini V, Meschi S, Lapa D, Haggiag S, Prosperini L, Cuzzi G, et al. Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose. International Journal of Molecular Sciences. 2023; 24(10):8525. https://doi.org/10.3390/ijms24108525
Chicago/Turabian StyleRuggieri, Serena, Alessandra Aiello, Carla Tortorella, Assunta Navarra, Valentina Vanini, Silvia Meschi, Daniele Lapa, Shalom Haggiag, Luca Prosperini, Gilda Cuzzi, and et al. 2023. "Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose" International Journal of Molecular Sciences 24, no. 10: 8525. https://doi.org/10.3390/ijms24108525