Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy
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Abstract
The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients.
Methods
We investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6–4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression.
Results
5.6 months (IQR: 5.1–6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0–7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants.
Conclusion
This study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.
Trial registration number
NCT04877496; ClinicalTrials.gov number.
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SciScore for 10.1101/2021.11.19.21266572: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was approved by the Ethics Committee of the Canton of Bern, Switzerland.
Consent: All participants provided written informed consent before inclusion.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis Statistical analysis: For this follow-up study, the initial RituxiVac study population was eligible without further power analysis or pre-screening procedures. Table 2: Resources
Antibodies Sentences Resources All study participants were tested for the presence of anti-nucleocapsid antibodies, and those with positive results were excluded from the analysis. anti-nucleocapsidsuggested: NoneBlood collection and measurement of … SciScore for 10.1101/2021.11.19.21266572: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was approved by the Ethics Committee of the Canton of Bern, Switzerland.
Consent: All participants provided written informed consent before inclusion.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis Statistical analysis: For this follow-up study, the initial RituxiVac study population was eligible without further power analysis or pre-screening procedures. Table 2: Resources
Antibodies Sentences Resources All study participants were tested for the presence of anti-nucleocapsid antibodies, and those with positive results were excluded from the analysis. anti-nucleocapsidsuggested: NoneBlood collection and measurement of anti-SARS-CoV-2 S1-IgG and NC-IgG: For the detection of SARS-CoV-2 specific antibodies, IgG antibodies against SARS-CoV-2 S1 protein were measured by a commercial ELISA from Euroimmun AG, Lübeck, Germany as previously reported13. anti-SARS-CoV-2suggested: NoneS1-IgGsuggested: NoneSARS-CoV-2 specific antibodies, IgGsuggested: NoneSARS-CoV-2 S1 proteinsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The present study has some limitations. First, while we observed a decline of circulating antibodies, this is a natural phenomenon because SARS-CoV-2 specific T and B memory cells persist within lymph nodes.20 Hence, an assessment of cell-mediated immunity would give additional insight to determine longer-lasting immune responses in anti-CD20 patients as described in a first report.21 Next, the present analysis did not include enough longitudinal measurements to allow for an in-depth modeling of the antibody decay dynamics that has been demonstrated in SARS-CoV-2 infection studies 22,23 or in selected reports of vaccinated healthy volunteers.19 With better understanding of the concentrations of circulating or neutralizing antibodies required for protection of severe disease in immunocompromised patients are understood like in the general population,24 prediction models based on neutralizing or total anti-spike antibody clearance rates and circulating peripheral immune cells could guide the administration of future vaccine doses. This is essential, because the heterogeneity of patients with anti-CD20 therapies and their immune response, the differences in their comorbidities, co-immunosuppression and in their environmental exposure to COVID-19 hinder the establishment of a simple generic algorithm for SARS-CoV-2 vaccination in this population. We therefore recommend to closely observe this population and invest in targeted public health strategies for different subsets of immu...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04877496 Recruiting Responses to COVID19 Vaccination in Patients With a Treatmen… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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