Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy

Moor, Matthias B.; Suter‐Riniker, Franziska; Horn, Michael P.; Aeberli, Daniel; Amsler, Jennifer; Moeller, B.; Njue, Linet M; Medri, Cesare; Angelillo‐Scherrer, Anne; Borradori, Luca; Radonjic-Hoesli, Susanne; Jafari, Morteza; Chan, Andrew; Hoepner, Robert; Bacher, Vera Ulrike; Mani, Laila-Yasmin; Iype, Joseena; Hirzel, Cédric; Maurer, Britta; Sidler, Daniel

doi:10.1101/2021.07.04.21259848

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…We show that the humoral response strongly correlates with B-cell counts and the interval between last anti-CD20 antibody administration and vaccination. Both, time from Rituximab to humoral response and CD19 counts necessary for vaccination response, are similar to results reported in parallel studies [15][16][17][18][19][20]. This provides crucial information on how to time anti-CD20 antibody application and SARS-CoV-2 vaccinations.…”

Section: Discussionsupporting

confidence: 80%

Response to SARS-CoV-2 vaccines in patients receiving B-cell modulating antibodies for renal autoimmune disease

et al. 2022

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Background Effective SARS-CoV-2 vaccination in patients receiving treatment with B-cell depleting agents is challenging. Information on vaccination responses in these patients are a valuable tool to develop efficient vaccination regimens. Methods In this single-center retrospective observational study, we report the humoral and cellular response in 34 patients receiving anti-CD20 antibody treatment for renal immune disease. Results After base immunization with SARS-CoV-2-vaccines, 92.0% developed a cellular, 32.4% a humoral response. Humoral immunity correlated with B-cell counts and the timespan between anti-CD20 antibody treatment and vaccination. All patients with > 21/µl B-cells, or > 197 days after treatment showed humoral response. Conclusions Adequate timing of SARS-CoV-2-vaccinations after anti-CD20 antibody treatment and CD19 measurements are crucial to generate immunity. Awaiting partial B-cell recovery by postponing regularly scheduled anti-CD20 treatment should be considered in patients with stable immune disease. Trial registration: This study has been retrospectively registered in the German Clinical Trials Register (DRKS00027049) on 29/10/2021.

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Section: Discussionsupporting

confidence: 80%

Response to SARS-CoV-2 vaccines in patients receiving B-cell modulating antibodies for renal autoimmune disease

et al. 2022

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“…Consistently with the previous literature,19 the time interval between RTX administration and vaccination was shown to be significant factors for the development of a humoral response to vaccination, and, thus, should be considered in vaccination planning. While B-cell repopulation represents another significant factor for a positive response to vaccination in RTX-treated patients,22 23 in our study, there was only a numeric difference in the CD19 cell counts in favour of responders. This is most likely related to a small size of this subgroup.…”

Section: Discussioncontrasting

confidence: 49%

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study

et al. 2022

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ObjectivesTo evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.MethodsA prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2–6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2–6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2–6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1.ConclusionsThe two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.

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“…The interval between the first and second vaccine dose was 3 weeks in most cases, and the interval between vaccination and serological diagnosis was 1-8 weeks. Of the 23 included studies, one (Speer et al, 2021) explicitly excluded those infected with COVID-19 after vaccination, seven (Palich et al, 2021a;Massarweh et al, 2021;Rabinowich et al, 2021;Sattler et al, 2021;Stumpf et al, 2021;Tzioufas et al, 2021;Shem-Tov et al, 2022) used nucleic acid testing to ensure that the included subjects were not infected with COVID-19 prior to vaccination, five (Grupper et al, 2021b;Goupil et al, 2021;Monin et al, 2021;Yanay et al, 2021;Ligumsky et al, 2022) documented subjects with asymptomatic or symptomatic infection after vaccination, and nine (Grupper et al, 2021a;Palich et al, 2021b;Geisen et al, 2021;Korth et al, 2021;Levy et al, 2021;Moor Frontiers in Pharmacology frontiersin.org et al, 2021;Tzioufas et al, 2021;Waissengrin et al, 2021;Waldhorn et al, 2021) included a statement that the included subjects did not have COVID-19 prior to vaccination. Most studies measured the post-vaccine humoral immune response using an enzyme-linked immunosorbent assay (ELISA) or LIAISON.…”

Section: Study Characteristicsmentioning

confidence: 99%

COVID-19 vaccination effectiveness and safety in vulnerable populations: a meta-analysis of 33 observational studies

Yang

Yao

et al. 2023

Front. Pharmacol.

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Background: Even 3 years into the COVID-19 pandemic, questions remain about how to safely and effectively vaccinate vulnerable populations. A systematic analysis of the safety and efficacy of the COVID-19 vaccine in at-risk groups has not been conducted to date.Methods: This study involved a comprehensive search of PubMed, EMBASE, and Cochrane Central Controlled Trial Registry data through 12 July 2022. Post-vaccination outcomes included the number of humoral and cellular immune responders in vulnerable and healthy populations, antibody levels in humoral immune responders, and adverse events.Results: A total of 23 articles assessing 32 studies, were included. The levels of IgG (SMD = −1.82, 95% CI [−2.28, −1.35]), IgA (SMD = −0.37, 95% CI [−0.70, −0.03]), IgM (SMD = −0.94, 95% CI [−1.38, −0.51]), neutralizing antibodies (SMD = −1.37, 95% CI [−2.62, −0.11]), and T cells (SMD = −1.98, 95% CI [−3.44, −0.53]) were significantly lower in vulnerable than in healthy populations. The positive detection rates of IgG (OR = 0.05, 95% CI [0.02, 0.14]) and IgA (OR = 0.03, 95% CI [0.01, 0.11]) antibodies and the cellular immune response rates (OR = 0.20, 95% CI [0.09, 0.45]) were also lower in the vulnerable populations. There were no statistically significant differences in fever (OR = 2.53, 95% CI [0.11, 60.86]), chills (OR = 2.03, 95% CI [0.08, 53.85]), myalgia (OR = 10.31, 95% CI [0.56, 191.08]), local pain at the injection site (OR = 17.83, 95% CI [0.32, 989.06]), headache (OR = 53.57, 95% CI [3.21, 892.79]), tenderness (OR = 2.68, 95% CI [0.49, 14.73]), and fatigue (OR = 22.89, 95% CI [0.45, 1164.22]) between the vulnerable and healthy populations.Conclusion: Seroconversion rates after COVID-19 vaccination were generally worse in the vulnerable than healthy populations, but there was no difference in adverse events. Patients with hematological cancers had the lowest IgG antibody levels of all the vulnerable populations, so closer attention to these patients is recommended. Subjects who received the combined vaccine had higher antibody levels than those who received the single vaccine.

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Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy

Cited by 8 publications

References 31 publications

Response to SARS-CoV-2 vaccines in patients receiving B-cell modulating antibodies for renal autoimmune disease

Response to SARS-CoV-2 vaccines in patients receiving B-cell modulating antibodies for renal autoimmune disease

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study

COVID-19 vaccination effectiveness and safety in vulnerable populations: a meta-analysis of 33 observational studies

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