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B cell depleting antibodies block COVID-19 vaccination even after three rounds.

Posted on December 24, 2025 by
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As we edge towards chrimbo day, I thought I would give you this info that people on B cell depleting antibodies make a blunted/limited vaccine response and this persists up to three rounds of vaccine. I guess this is a bit of a NSS moment….We reported the issue of blunting of vaccine response in ocrelizumab-treated people many moons ago… I haven’t done a COVID-19 post in months years and this one tickled me. I am sure you are a bit like me and have rather forgotten about COVID-19…I have been had COVID about 3 or 4 different times now……We still vaccinate immunosuppressed and older people who are more likely to have a senile immune systems……So what does the paper say?…

It says

  • “This study demonstrates that pwMS on non-B Cell Depleting Therapy (BCDT) mount vaccine responses comparable to healthy adults, while pwMS on B cell depleting therapies have persistently lower neutralizing antibodies following a third COVID-19 vaccine dose.
  • Importantly, reduced antibody titres (levels) in pwMS on BCDT did not translate into increased risk of COVID-19 hospitalisation, suggesting partial protection was maintained.
  • The study also provides novel evidence of cross-reactive neutralising activity in pwMS sera collected before COVID-19 emerged, implying a potential role for pre-existing coronavirus immunity”.

Yep NSS……if you have been following the blog you will know this already and maybe you have forgotten it as you knew so long ago

The message….There is cross-reactivity of antibodies with past corona virus and people on anti-CD20 did not get hospitalisations in this cohort and I have to laugh as there was no mention of T cells. What happened to the usual Scroogey Referee making you mention T cells when you talk about B cell depleting therapy?.

… A B cell depleting paper in MS and no mention of T cells….It made my day….But the authors forgot to mention and that vaccination generates protective anti-viral T cell responses in B cell depleted people. Maybe this contributes to infection control.So the referees did a stellar job:-).

They tested reactions to alot of different strains using live viral assays which is alot of work, ProfA could knock these assays out as fast a you could find the virus sequences

Shawe-Taylor MJ, Greenwood D, He A, Hobbs A, Dowgier G, Penn R, Sanderson T, Stevenson-Leggett P, Bazire J, Harvey R, Champsas D, Sharmin S, Aojula A, Bianchi A, Al-Araji S, Hacohen Y, Yam C, Mohamud S, Christensen R, Moccia M; Crick COVID Serology Pipeline; Legacy Investigators; Libri V, Kassiotis G, Gamblin S, Lewis N, Williams B, Swanton C, Gandhi S, Bauer D, Wu M, Carr E, Wall E, Ciccarelli O. Immunogenicity of three-dose COVID-19 vaccines in people living with multiple sclerosis. BMJ Neurol Open. 2025 ;7(2):e001210.

Introduction: People with multiple sclerosis (pwMS) receiving B-cell depleting disease-modifying therapy (BCD-DMT) are vulnerable to severe COVID-19. Data on vaccine immunogenicity in this patient group are incomplete. In the context of the rapid evolution of SARS-CoV-2 2020-22, we compared vaccine responses in pwMS and healthy vaccinated adults (HVA) after three doses of messenger RNA vaccine encoding Ancestral SARS-CoV-2 Spike.

Methods: In this prospective observational cohort study, we collected serum from 226 pwMS prevaccine and postvaccine and quantified neutralising antibody titres (nAbT) in a high-throughput live virus assay against SARS-CoV-2 Ancestral, Alpha, Delta, Omicron BA.1, BA.2 and BA.5. We compared nAbT in pwMS and HVA, matched by age, sex, vaccine type, number of doses and time since exposure, using Wilcoxon signed-rank and χ2 tests. We further investigated nAbT vaccine response in pwMS on BCD-DMTs or non-depleting DMTs.

Results: Prior to third vaccination, nAbTs against nearly all variants tested were significantly lower (p<0.05) in pwMS taking BCD therapy than those in HVA or B-cell replete pwMS, and were not significantly boosted following vaccination. In contrast, B-cell replete pwMS versus HVAs exhibited equivalent prevaccination nAbTs against all variants, which were comparably boosted against most variants following vaccination. Consequently, differences in nAbTs against all variants tested were further magnified between B-cell replete and B-cell depleted pwMS post-third vaccination. Across the entire cohort, there were no COVID-19 hospitalisations or deaths. Notably, sera collected prior to the pandemic from pwMS demonstrated pre-existing, pan-coronavirus neutralising activity against seasonal HCoV-OC43 and SARS-CoV-2 variants.

Conclusions: PwMS taking BCD therapy have limited antibody boosting following repeated COVID-19 vaccination. However, the absence of severe outcomes in pwMS, despite reduced immunogenicity, suggests a lower threshold for effective protection than previously reported. These findings support more nuanced risk stratification in clinical policy.

Source: multiple-sclerosis-research.org

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