SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response

Bonelli, Michael; Mrak, Daniel; Perkmann, Thomas; Haslacher, Helmuth; Aletaha, Daniel

doi:10.1136/annrheumdis-2021-220408

Cited by 147 publications

(152 citation statements)

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“…However, it remains unclear whether, or to which extent, repopulation of peripheral B cells is needed for antibody development in RTX-treated patients. 15 To determine if or for how long it might be useful to withhold COVID-19 vaccination in RTX-treated patients, we assessed the cellular and humoral immune response and related it to numbers of peripheral B cells.…”

Section: Miscellaneousmentioning

confidence: 99%

SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity

et al. 2021

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ObjectivesEvidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation.MethodsPatients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls.ResultsAll healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response.ConclusionsThe data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.

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Section: Miscellaneousmentioning

confidence: 99%

SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity

et al. 2021

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“…Indeed, available data are still too limited to suggest treatment discontinuation in order to favor a vaccination response, considering the significant risk of clinical relapse and MRI activity associated to second-line treatment withdrawal (at least in relapsing–remitting MS patients). Furthermore, initial reports relative to other medical conditions causing immunodeficiency suggest the possibility of an efficient cell-mediated immunity after vaccination even in the absence of a detectable humoral response [ 10 ].…”

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Serological response to SARS-CoV-2 vaccination in multiple sclerosis patients treated with fingolimod or ocrelizumab: an initial real-life experience

et al. 2021

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Background Recent observations suggest a lack of humoral response after SARS-CoV-2 vaccination in multiple sclerosis (MS) patients treated with fingolimod or ocrelizumab Objectives To assess serological response to SARS-CoV-2 vaccination in MS patients receiving these disease-modifying treatments (DMTs) in a real-life setting. Methods Retrospective clinical data collection from MS patients followed at San Raffaele Hospital MS Centre (Milan, Italy). All patients treated with fingolimod or ocrelizumab who had received a complete anti-COVID-19 vaccination course, with no clinical history suggestive of previous SARS-CoV-2 infection and with an available post-vaccination serological assay obtained at least 14 days after vaccination completion were considered for the study. Results We collected data from 32 MS patients, 16 treated with fingolimod and 16 receiving ocrelizumab. Among the fingolimod group 10 patients (62.5%) had a positive serological response after vaccination and among ocrelizumab-treated patients a positive serological test was found in six cases (37.5%). No relation between serological response and clinical features (i.e., treatment duration, time between vaccination and last treatment dose, and white blood cells count) was identified. Conclusions Our initial real-life experience suggests a variable antibody production in MS patients receiving these DMTs. At present, there are no sufficient data to do not recommend anti-SARS-CoV-2 vaccine in these patients.

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“…We read with a great interest the article published by Bonelli et al suggesting an inducible cellular immune response in rituximab (Rtx) treated patients. 1 The CD20-antibody Rtx is one of the most widespread biologicals worldwide with a broad spectrum of oncological and rheumatological indications. Due to its depleting effect on circulating B cells, the generation of antibodies against novel pathogens is impaired in Rtx-treated patients.…”

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“…7 Fortunately, very recent data by Bonelli et al have now suggested that a cellular response is mounted after SARS-CoV-2 vaccination in Rtxtreated patients despite a failed humoral immune response. 1 The authors demonstrated that peripheral blood cells of vaccinated patients do produce Interferon γ (IFNγ) after stimulation with SARS-CoV-2 spike (S) protein-derived overlapping peptides. 1 These results increase the scientific interest into a more detailed characterisation of vaccine-reactive T-cell immunity, which has recently been in the focus of our group as well due to a frequent Rtx application in our settings.…”

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The role of SARS-CoV-2-specific antibodies in COVID-19 is not well established: reports indicate an increased risk of severe COVID-19 infections in Rtx-treated patients, 7 whereas other data have suggested that B cells are dispensable for resolving such infections. 11 The here presented data indicate that polyfunctional antiviral T cell responses are raised after SARS-CoV-2 vaccination in this high-risk population suggesting protection in the absence of virus-specific antibodies.

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SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response

Abstract: Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Cited by 147 publications

References 6 publications

SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity

SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity

Serological response to SARS-CoV-2 vaccination in multiple sclerosis patients treated with fingolimod or ocrelizumab: an initial real-life experience

Correspondence on ‘SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response’

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