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

Hamza Mahmood Bajwa, Frederik Novak, Anna Christine Nilsson, Christian Nielsen, Dorte K. Holm, Kamilla Østergaard, Agnes Hauschultz Witt, Keld Erik Byg, Isik S. Johansen, Kristen Mittl, William Rowles, Scott S. Zamvil, Riley Bove, Joseph J. Sabatino, Tobias Sejbaek*

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Abstrakt

Objective: To examine humoral and cellular response in multiple sclerosis patients on anti-CD20 therapy after third BNT162b2 mRNA SARS-CoV-2 vaccination. Methods: 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). Results: 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). Conclusion: 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.

OriginalsprogEngelsk
Artikelnummer103729
TidsskriftMultiple Sclerosis and Related Disorders
Vol/bind60
ISSN2211-0348
DOI
StatusUdgivet - apr. 2022

Bibliografisk note

Funding Information:
T Sejbaek has received travel grants from Biogen, Merck, Novartis, and Roche, has received research grants from Biogen and has served on advisory boards for Biogen, Merck, and Novartis.

Funding Information:
We acknowledge the great help received from patients participating in this trial and our team of technicians and study coordinators represented by Gunhild Brixen 1 Nielsen, Sarah Andersen 1, and Pia Hannesbo 6 . We acknowledge grants given by the Lundbeck Neurological Scholarship delegated by the Danish Neurological Society and by Roche.

Funding Information:
R Bove has received research support from Biogen , Roche Genentech, and Novartis. She has received personal consulting fees from Alexion, Biogen, EMD Serono, Novartis, Roche Genentech, and Sanofi Genentech. She is funded by Harry Weaver Award from the National Multiple Sclerosis Society and the National Institutes of Health .

Funding Information:
We acknowledge the great help received from patients participating in this trial and our team of technicians and study coordinators represented by Gunhild Brixen1 Nielsen, Sarah Andersen1, and Pia Hannesbo6. We acknowledge grants given by the Lundbeck Neurological Scholarship delegated by the Danish Neurological Society and by Roche. H Bajwa, F Novak, A C Nilsson, KE Byg, I S Johansen, C Nielsen, D K Holm, A B Jacobsen, K Mittl, and W Rowles have nothing to disclose. J Sabatino has received research support from Novartis. R Bove has received research support from Biogen, Roche Genentech, and Novartis. She has received personal consulting fees from Alexion, Biogen, EMD Serono, Novartis, Roche Genentech, and Sanofi Genentech. She is funded by Harry Weaver Award from the National Multiple Sclerosis Society and the National Institutes of Health. SS Zamvil has received consulting honoraria from Alexion, Biogen-Idec, EMD-Serono, Genzyme, Novartis, Roche/Genentech, and Teva Pharmaceuticals, Inc and has served on Data Safety Monitoring Boards for Lilly, BioMS, Teva, and Therapeutics. T Sejbaek has received travel grants from Biogen, Merck, Novartis, and Roche, has received research grants from Biogen and has served on advisory boards for Biogen, Merck, and Novartis. H Bajwa, F Novak, T Sejbaek, J Sabatino, I S Johansen, KE Byg, and R Bove all contributed to study design, H Bajwa, F Novak, T Sejbaek, J Sabatino, W Rowles, AH Witt, K ?stergaard all contributed to patient recruitment and patient data, F Novak, T Sejbaek, J Sabatino, A C Nilsson, C Nielsen, K Mittl, and W Rowles all contributed to sample processing, H Bajwa, F Novak, T Sejbaek, J Sabatino, A C Nilsson, C Nielsen, I S Johansen, KE Byg, AH Witt, K ?stergaard, S Zamvil, and R Bove all contributed to data analysis/interpretation

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