Determining the best window for BNT162b2 mRNA vaccination for SARS-CoV-2 in patients with multiple sclerosis receiving anti-CD20 therapy

Abstract

We studied the serologic response to the BNT162b2 mRNA vaccine at four weeks after the second dose in patients with RRMS treated with rituximab with extended-interval dosing ( n = 26). At four weeks, 73% of patients were seropositive. No patient without B cells at the first dose ( n = 4) was seropositive. Four of seven (57%) patients with B-cell proportion >0% and ≤5% were seropositive. All patients with B-cell proportion >5% ( n = 15) were seropositive. In all patients, quantitative ELISA measures after vaccination were correlated with B-cell counts measured before vaccination. In patients receiving rituximab, seropositivity after BNT162b2 mRNA vaccination emerged only after B-cell repopulation.

Immune responses to SARS‐CoV‐2 vaccination in multiple sclerosis: a systematic review/meta‐analysis

“…Some studies report that the timing of vaccination versus infusion affects the likelihood of seropositivity, whereas others do not. The presence of CD19 + and/or CD20 + cells were associated with an increased likelihood of antibody response in some studies 9–12,16,17 but not in others 18,19,36 ; the presence of CD19 + /CD20 + cells is somewhat correlated with timing 11,15,17,19,50 but was not consistently in all patients 16 …”

“…1 ). 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 …”

B‐cell repopulation dynamics and drug pharmacokinetics impact SARS‐CoV‐2 vaccine efficacy in anti‐CD20‐treated multiple sclerosis patients

“…With the outbreak of the COVID‐19 pandemic, concerns were raised regarding the impact of BCDTs on humoral and cellular immune response to SARS‐CoV‐2 infection and vaccination [ 3 ]. Since then, several studies have reported a blunted antibody response, albeit a largely intact T‐cell response, in persons with MS (pwMS) treated with BCDTs [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 ]. Failure to seroconvert has in particular been observed in pwMS who received an anti‐CD20 infusion close to the time of vaccination [ 4 , 13 ].…”

“…Although a correlation between time since last dose and B‐cell repletion exists at the group level, variable total treatment duration and individual differences may impact on B‐cell repopulation dynamics [ 17 ]. Therefore, an ideal dosing interval to optimize vaccine response that fits all patients seems unlikely, and there is a need for robust biomarkers that can predict vaccine efficacy while maintaining the effect of anti‐CD20 treatment on relapse rates [ 10 , 12 ].…”

Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes

“…Previous studies have shown that even minimal B-cell reconstitution may correlate with an increased humoral response to COVID-19 vaccination. ( Disanto et al, 2021 , Apostolidis et al, 2021 , Rico et al, 2021 , van Kempen et al, 2021 ) In one study, while 1 of 36 patients with undetectable B cells seroconverted after vaccination, 45% of patients with between 0 and 1% of CD19+ B cells seroconverted. ( Mrak et al, 2021 ) Studies have also found a significant correlation between time since last anti-CD20 infusion as well as length of anti-CD20 therapy and SARS-CoV-2 antibody titer.…”