Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy
Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: Sixty-four patients who received Rituximab within the last seven years p...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/6/1739 |
| _version_ | 1797470427314913280 |
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| author | Maximilian Töllner Claudius Speer Louise Benning Marie Bartenschlager Christian Nusshag Christian Morath Martin Zeier Caner Süsal Paul Schnitzler Wilhelm Schmitt Raoul Bergner Ralf Bartenschlager Hanns-Martin Lorenz Matthias Schaier |
| author_facet | Maximilian Töllner Claudius Speer Louise Benning Marie Bartenschlager Christian Nusshag Christian Morath Martin Zeier Caner Süsal Paul Schnitzler Wilhelm Schmitt Raoul Bergner Ralf Bartenschlager Hanns-Martin Lorenz Matthias Schaier |
| author_sort | Maximilian Töllner |
| collection | DOAJ |
| description | Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: Sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19<sup>+</sup> peripheral B-cells were quantified using flow cytometry. Results: After second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID<sub>50</sub> of 0 (0–1:20) compared to 1:320 (1:160–1:320) in healthy controls (for all <i>p</i> < 0.001). Longer time period since last Rituximab administration correlated with higher anti-SARS-CoV-2 antibody levels and a stronger neutralization of B.1.617.2 (delta). With one exception, only patients with a CD19<sup>+</sup> cell proportion ≥ 1% had detectable neutralizing antibodies. Conclusion: Our data indicate that a reconstitution of the B-cell population to >1% seems crucial in developing neutralizing antibodies against SARS-CoV-2. We suggest that anti-SARS-CoV-2 vaccination should be administered at least 8–12 months after the last Rituximab treatment for sufficient humoral responses. |
| first_indexed | 2024-03-09T19:36:11Z |
| format | Article |
| id | doaj.art-082f4f7b98164ca3852bdcf822dd60a7 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T19:36:11Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-082f4f7b98164ca3852bdcf822dd60a72023-11-24T01:51:56ZengMDPI AGJournal of Clinical Medicine2077-03832022-03-01116173910.3390/jcm11061739Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 TherapyMaximilian Töllner0Claudius Speer1Louise Benning2Marie Bartenschlager3Christian Nusshag4Christian Morath5Martin Zeier6Caner Süsal7Paul Schnitzler8Wilhelm Schmitt9Raoul Bergner10Ralf Bartenschlager11Hanns-Martin Lorenz12Matthias Schaier13Department of Nephrology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Nephrology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Nephrology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Nephrology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Nephrology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Nephrology, University of Heidelberg, 69120 Heidelberg, GermanyTransplant Immunology Research Center of Excellence, Koç University Hospital, Istanbul 34010, TurkeyDepartment of Infectious Diseases, Virology, University of Heidelberg, 69120 Heidelberg, GermanyCenter for Renal Diseases, 69469 Weinheim, GermanyClinical Center Ludwigshafen, Department of Internal Medicine A, 67036 Ludwigshafen, GermanyDepartment of Infectious Diseases, Molecular Virology, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Rheumatology, Department of Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Nephrology, University of Heidelberg, 69120 Heidelberg, GermanyBackground: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: Sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19<sup>+</sup> peripheral B-cells were quantified using flow cytometry. Results: After second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID<sub>50</sub> of 0 (0–1:20) compared to 1:320 (1:160–1:320) in healthy controls (for all <i>p</i> < 0.001). Longer time period since last Rituximab administration correlated with higher anti-SARS-CoV-2 antibody levels and a stronger neutralization of B.1.617.2 (delta). With one exception, only patients with a CD19<sup>+</sup> cell proportion ≥ 1% had detectable neutralizing antibodies. Conclusion: Our data indicate that a reconstitution of the B-cell population to >1% seems crucial in developing neutralizing antibodies against SARS-CoV-2. We suggest that anti-SARS-CoV-2 vaccination should be administered at least 8–12 months after the last Rituximab treatment for sufficient humoral responses.https://www.mdpi.com/2077-0383/11/6/1739COVID-19Rituximabvaccination |
| spellingShingle | Maximilian Töllner Claudius Speer Louise Benning Marie Bartenschlager Christian Nusshag Christian Morath Martin Zeier Caner Süsal Paul Schnitzler Wilhelm Schmitt Raoul Bergner Ralf Bartenschlager Hanns-Martin Lorenz Matthias Schaier Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy Journal of Clinical Medicine COVID-19 Rituximab vaccination |
| title | Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy |
| title_full | Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy |
| title_fullStr | Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy |
| title_full_unstemmed | Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy |
| title_short | Impaired Neutralizing Antibody Activity against B.1.617.2 (Delta) after Anti-SARS-CoV-2 Vaccination in Patients Receiving Anti-CD20 Therapy |
| title_sort | impaired neutralizing antibody activity against b 1 617 2 delta after anti sars cov 2 vaccination in patients receiving anti cd20 therapy |
| topic | COVID-19 Rituximab vaccination |
| url | https://www.mdpi.com/2077-0383/11/6/1739 |
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