Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD20 therapy
Copyright © 2024 Priddey, Chen-Xu, Cooper, MacMillan, Meisl, Xu, Hosmillo, Goodfellow, Kollyfas, Doffinger, Bradley, Mohorianu, Jones, Knowles, Smith and Kosmoliaptsis..
Background: Patients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely, affinity and concentration, shape the quality of humoral immunity after vaccination in these patients.
Methods: We performed in-depth antibody characterisation in sera collected 4 to 6 weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in rituximab-treated primary vasculitis patients (n = 14) using Luminex and pseudovirus neutralisation assays, whereas we used a novel microfluidic-based immunoassay to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. We performed comparative antibody profiling at equivalent timepoints in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n = 15) and in convalescent patients after WT SARS-CoV-2 infection (n = 30).
Results: Rituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in rituximab-treated patients and in healthy individuals. In the rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT [median (range) KD: 21.6 (9.7-38.8) nM vs. 4.6 (2.3-44.8) nM, p = 0.0004]. By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in rituximab-treated patients [median (range) KD: 1.05 (0.45-1.84) nM vs. 20.25 (13.2-38.8) nM, p = 0.0002], underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection, which was not observed in rituximab-treated patients, despite repeated vaccination.
Discussion: Our results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 22., Seite 1296148 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Priddey, Ashley [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.01.2024 Date Revised 01.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.1296148 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Priddey, Ashley |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD20 therapy |
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| 500 | |a Date Revised 01.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Priddey, Chen-Xu, Cooper, MacMillan, Meisl, Xu, Hosmillo, Goodfellow, Kollyfas, Doffinger, Bradley, Mohorianu, Jones, Knowles, Smith and Kosmoliaptsis. | ||
| 520 | |a Background: Patients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely, affinity and concentration, shape the quality of humoral immunity after vaccination in these patients | ||
| 520 | |a Methods: We performed in-depth antibody characterisation in sera collected 4 to 6 weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in rituximab-treated primary vasculitis patients (n = 14) using Luminex and pseudovirus neutralisation assays, whereas we used a novel microfluidic-based immunoassay to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. We performed comparative antibody profiling at equivalent timepoints in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n = 15) and in convalescent patients after WT SARS-CoV-2 infection (n = 30) | ||
| 520 | |a Results: Rituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in rituximab-treated patients and in healthy individuals. In the rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT [median (range) KD: 21.6 (9.7-38.8) nM vs. 4.6 (2.3-44.8) nM, p = 0.0004]. By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in rituximab-treated patients [median (range) KD: 1.05 (0.45-1.84) nM vs. 20.25 (13.2-38.8) nM, p = 0.0002], underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection, which was not observed in rituximab-treated patients, despite repeated vaccination | ||
| 520 | |a Discussion: Our results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Omicron (B.1.1.529) | |
| 650 | 4 | |a SARS-CoV-2 infection | |
| 650 | 4 | |a SARS-CoV-2 vaccination | |
| 650 | 4 | |a antibody affinity | |
| 650 | 4 | |a antibody concentration | |
| 650 | 4 | |a immunocompromised | |
| 650 | 4 | |a neutralisation capacity | |
| 650 | 4 | |a rituximab | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a Rituximab |2 NLM | |
| 650 | 7 | |a 4F4X42SYQ6 |2 NLM | |
| 650 | 7 | |a Antibodies |2 NLM | |
| 700 | 1 | |a Chen-Xu, Michael Xin Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, Daniel James |e verfasserin |4 aut | |
| 700 | 1 | |a MacMillan, Serena |e verfasserin |4 aut | |
| 700 | 1 | |a Meisl, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Catherine K |e verfasserin |4 aut | |
| 700 | 1 | |a Hosmillo, Myra |e verfasserin |4 aut | |
| 700 | 1 | |a Goodfellow, Ian G |e verfasserin |4 aut | |
| 700 | 1 | |a Kollyfas, Rafael |e verfasserin |4 aut | |
| 700 | 1 | |a Doffinger, Rainer |e verfasserin |4 aut | |
| 700 | 1 | |a Bradley, John R |e verfasserin |4 aut | |
| 700 | 1 | |a Mohorianu, Irina I |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Knowles, Tuomas P J |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Rona |e verfasserin |4 aut | |
| 700 | 1 | |a Kosmoliaptsis, Vasilis |e verfasserin |4 aut | |
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