#MSCOVID19 vaccination. Yet another …….Guess what? Yep CD20-depleting antibodies inhibit antibody responses but there is a robust T cell response

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So I think we can be confident that the headline is the reality. We have seen this over and over again and we will see it again and again.. It is amazing that fingolimod studies are yet to surface However…….

Now what we need to know is…Is this important is there sufficient protection. Based on immunology 101 if the antibody levels are low then the capacity to stop the development of symptomatic COVID is likely to be reduced. However the T cells may take up the slack but how good is this going to be.

Brill L, Rechtman A, Zveik O, Haham N, Oiknine-Djian E, Wolf DG, Levin N, Raposo C, Vaknin-Dembinsky A. Humoral and T-Cell Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Ocrelizumab. JAMA Neurol. 2021 Sep 23. doi: 10.1001/jamaneurol.2021.3599.

This is Brill et al. 2021

Importance: B-cell-depleting therapies may affect the development of a protective immune response following vaccination. Understanding the ability to develop vaccine-specific immunity to COVID-19 in patients with multiple sclerosis (MS) treated with B-cell-depleting therapy is of importance for clinical decisions.

Objective: To assess SARS-CoV-2 vaccine-specific humoral and cellular responses in patients treated with ocrelizumab compared with healthy controls.

Design, setting, and participants: This single-center study performed at Hadassah Medical Center in Jerusalem, Israel, included patients with MS treated with ocrelizumab, healthy controls, and untreated patients with MS. Vaccination occurred between December 2020 and April 2021. Participants donated blood 2 to 4 and 2 to 8 weeks after the second vaccine dose for antibody and T-cell assessments, respectively.

Exposures: All participants received 2 doses of BNT162b2 vaccine (Pfizer/BioNTech) and completed the study.

Main outcomes and measures: Proportion of patients treated with ocrelizumab with SARS-CoV-2-specific serology and/or T-cell responses following vaccination. All participants underwent SARS-CoV-2 antibody testing; 29 patients treated with ocrelizumab and 15 healthy controls had evaluation of SARS-CoV-2-specific T-cell responses.

Results: Of 112 participants, 49 (43.8%) had MS and were treated with ocrelizumab (33 [67.3%] female; mean [SD] age, 47.9 [13.3] years), 23 (20.5%) had MS and were not treated with disease-modifying therapies (18 [78.3%] female; mean [SD] age, 49 [13.4] years), and 40 (35.7%) were healthy controls (25 [62.5%] female; mean [SD] age, 45.3 [16] years). Twenty-six of 29 patients (89.7%) treated with ocrelizumab and 15 of 15 healthy controls (100%) had SARS-CoV-2-specific T cells following vaccination at similar levels (mean [SD], 15.4 [7.6] and 14.3 [6.3] spot-forming cells, respectively). Mean antibody titers and positive serology rate were lower in the group of patients treated with ocrelizumab (mean [SD] antibody titers and positive serology rate, 26.2 [49.2] and 376.5 [907.6] AU/mL; 10 of 40 [25%] and 20 of 49 [40.8%] for S1/S2 and receptor-binding domain, respectively) compared with healthy controls (mean [SD] antibody titers and positive serology rate, 283 [100] and 12 712 [9114] AU/mL; 100% S1/S2 and receptor-binding domain) and untreated patients (mean [SD] antibody titers and positive serology rate, 288.3 [113.8] and 10 877 [9476] AU/mL; 100% S1/S2 and receptor-binding domain), with positive association to time from ocrelizumab infusion (S1/S2: r = 0.7, P < .001; receptor-binding domain: r = 0.4, P = .04).

Conclusion and relevance: In this study, patients with MS who were treated with ocrelizumab generated comparable SARS-CoV-2-specific T-cell responses with healthy controls and had lower antibody response following vaccination. Given the potential role of T cells in protection from severe disease, this is reassuring and will help physicians develop consensus guidelines regarding MS treatment in the era of the COVID-19 pandemic.

Draw a line up from 6 months on the vaccination before 6 months and seroconversion it is about 5/21 (24%), do it after it is about 6/11 (54%) do it after 9 months it is about 3/4 (75%).

Is the writing on the wall getting bigger?

Disanto G, Sacco R, Bernasconi E, Martinetti G, Keller F, Gobbi C, Zecca C. Association of Disease-Modifying Treatment and Anti-CD20 Infusion Timing With Humoral Response to 2 SARS-CoV-2 Vaccines in Patients With Multiple Sclerosis. JAMA Neurol. 2021 Sep 23. doi: 10.1001/jamaneurol.2021.3609

Ex-TeamG memeber G Disanto shows us a few things. (a) Many people on fingolimod make a response but it is very weak. This is what happened in the large Italian study. In contrast (b) CD20 depleters can block the response and (c) cladribine is good as is teri.

The longer the time interval between dosing of anti-CD20 and the vaccine the better the response and the more B cells the better the response.

Can we explain this, yes I think we can and it was submitted today. So in 3 -5 days you can have a read. Stay turned.

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