Immune response to SARS-CoV-2 vaccination in relation to peripheral immune cell profiles among patients with multiple sclerosis receiving ocrelizumab

Abstract

BackgroundVaccination has proven to be effective in preventing SARS-CoV-2 transmission and severe disease courses. However, immunocompromised patients have not been included in clinical trials and real-world clinical data point to an attenuated immune response to SARS-CoV-2 vaccines among patients with multiple sclerosis (MS) receiving immunomodulatory therapies.MethodsWe performed a retrospective study including 59 ocrelizumab (OCR)-treated patients with MS who received SARS-CoV-2 vaccination. Anti-SARS-CoV-2-antibody titres, routine blood parameters and peripheral immune cell profiles were measured prior to the first (baseline) and at a median of 4 weeks after the second vaccine dose (follow-up). Moreover, the SARS-CoV-2-specific T cell response and peripheral B cell subsets were analysed at follow-up. Finally, vaccination-related adverse events were assessed.ResultsAfter vaccination, we found anti-SARS-CoV-2(S) antibodies in 27.1% and a SARS-CoV-2-specific T cell response in 92.7% of MS cases. T cell-mediated interferon (IFN)-γ release was more pronounced in patients without anti-SARS-CoV-2(S) antibodies. Antibody titres positively correlated with peripheral B cell counts, time since last infusion and total IgM levels. They negatively correlated with the number of previous infusion cycles. Peripheral plasma cells were increased in antibody-positive patients. A positive correlation between T cell response and peripheral lymphocyte counts was observed. Moreover, IFN-γ release was negatively correlated with the time since the last infusion.ConclusionIn OCR-treated patients with MS, the humoral immune response to SARS-CoV-2 vaccination is attenuated while the T cell response is preserved. However, it is still unclear whether T or B cell-mediated immunity is required for effective clinical protection. Nonetheless, given the long-lasting clinical effects of OCR, monitoring of peripheral B cell counts could facilitate individualised treatment regimens and might be used to identify the optimal time to vaccinate.

Hypogammaglobulinemia is associated with reduced antibody response after anti-SARS-CoV-2 vaccination in MS patients treated with antiCD20 therapies

“…The association between higher EDSS and reduced response rate could be explained, at least in part, to the higher disability burden in patients treated with antiCD20 therapies, which indeed was the strongest predictor of reduced vaccine response. This finding is consistent with the available evidence [6,7,11,13,15]. Other studies have indicated the possibility of reduced response after fingolimod as well [16,20,34], while patients treated with cladribine were reported to have a good antibody response [12].…”

“…Our results indicated an increased prevalence of fatigue after vaccination compared with the general population, while the rates of the other reported AEs were comparable with that reported in the phase III RCTs of COVID-19 vaccines. Consistently, fatigue is one of the most frequent AEs after vaccination in MS patients reported in the literature [3,6,8,9,15,18].…”

“…The role of hypogammaglobulinemia as a factor influencing vaccination efficacy has not been fully elucidated. In previous studies on anti-SARS-CoV-2 vaccine response in MS patients receiving antiCD20 (ocrelizumab or ofatumumab), no association between Ig levels and ability to mount a humoral response was found [10,11,15,35]. Differences in size and characteristics of study samples could account for these inconsistencies.…”

“…In another study, focusing on 99 patients treated with antiCD20 therapies, a higher number of total infusions was associated with a lower probability of having an efficacious response at a binomial logistic regression analysis [9]. Other recent studies reported a negative correlation between treatment duration and lower Ab titer in patients treated with antiCD20 [15,18], without adjusting for other clinical and demographic factors. Finally, one study did not find any correlation between treatment duration and antibody response in MS patients treated with ocrelizumab [6].…”

“…As further confirmation, a recent prospective study including 324 patients with MS who received BNT162b2 vaccine did not disclose an increased risk of clinical relapses during the 2-month follow-up after the first vaccine dose [5]. Regarding efficacy, several studies have been conducted so far [6][7][8][9][10][11][12][13][14][15][16][17][18]. On the whole, these studies suggest a less robust immune response in patients treated with antiCD20 therapies [6,8,10,13,[17][18][19] and possibly fingolimod [19,20], while other DMTs, such as natalizumab [21] and cladribine [12], seemed to have no effect on vaccination response.…”