IgG1 responses following SARS-CoV-2 infection are polyclonal and highly personalized, whereby each donor and each clone displays a distinct pattern of cross-reactivity against SARS-CoV-2 variants
Abstract Using a recently introduced efficient mass spectrometry-based approach we monitored individual donors’ IgG1 clonal responses in molecular detail, examining SARS-CoV-2 spike-protein-specific IgG1 repertoires. We monitored the plasma clonal IgG1 profiles of 8 donors (4 male and 4 female) who had recently experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we charted the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer as antigen. We observed that shortly after infection in between <0.1% to almost 10% of all IgG1 antibody molecules present in plasma did bind to the spike protein. Each donor displayed a unique plasma IgG1 repertoire, but also each donor displayed a unique and polyclonal antibody response against the SARS-CoV-2 spike-protein variants. Our analyses revealed that certain clones exhibit (alike) binding affinity towards all four tested spike-protein variants, whereas other clones displayed strong unique mutant-specific affinity. We conclude that each infected person generates a unique polyclonal response following infection, whereby some of these clones can bind multiple viral variants, whereas other clones do not display such cross-reactivity. In general, by assessing IgG1 repertoires following infection it becomes possible to identify and select fully matured human plasma antibodies that target specific antigens, and display either high specificity or cross-reactivity versus mutated versions of the antigen, which will aid in selecting antibodies that may be developed into biotherapeutics..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 18. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
van Rijswijck, Danique M.H. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.02.24.481778 |
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| PPN (Katalog-ID): |
XBI035344040 |
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| 245 | 1 | 0 | |a IgG1 responses following SARS-CoV-2 infection are polyclonal and highly personalized, whereby each donor and each clone displays a distinct pattern of cross-reactivity against SARS-CoV-2 variants |
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| 520 | |a Abstract Using a recently introduced efficient mass spectrometry-based approach we monitored individual donors’ IgG1 clonal responses in molecular detail, examining SARS-CoV-2 spike-protein-specific IgG1 repertoires. We monitored the plasma clonal IgG1 profiles of 8 donors (4 male and 4 female) who had recently experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we charted the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer as antigen. We observed that shortly after infection in between <0.1% to almost 10% of all IgG1 antibody molecules present in plasma did bind to the spike protein. Each donor displayed a unique plasma IgG1 repertoire, but also each donor displayed a unique and polyclonal antibody response against the SARS-CoV-2 spike-protein variants. Our analyses revealed that certain clones exhibit (alike) binding affinity towards all four tested spike-protein variants, whereas other clones displayed strong unique mutant-specific affinity. We conclude that each infected person generates a unique polyclonal response following infection, whereby some of these clones can bind multiple viral variants, whereas other clones do not display such cross-reactivity. In general, by assessing IgG1 repertoires following infection it becomes possible to identify and select fully matured human plasma antibodies that target specific antigens, and display either high specificity or cross-reactivity versus mutated versions of the antigen, which will aid in selecting antibodies that may be developed into biotherapeutics. | ||
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| 700 | 1 | |a Bondt, Albert |0 (orcid)0000-0002-0985-7903 |4 aut | |
| 700 | 1 | |a Hoek, Max |4 aut | |
| 700 | 1 | |a van der Straten, Karlijn |0 (orcid)0000-0001-6373-9302 |4 aut | |
| 700 | 1 | |a Caniels, Tom G. |0 (orcid)0000-0001-9580-157X |4 aut | |
| 700 | 1 | |a Poniman, Meliawati |0 (orcid)0000-0001-8390-2058 |4 aut | |
| 700 | 1 | |a Eggink, Dirk |4 aut | |
| 700 | 1 | |a Reusken, Chantal |4 aut | |
| 700 | 1 | |a de Bree, Godelieve J. |0 (orcid)0000-0002-5852-5833 |4 aut | |
| 700 | 1 | |a Sanders, Rogier W. |4 aut | |
| 700 | 1 | |a van Gils, Marit J. |0 (orcid)0000-0003-3422-8161 |4 aut | |
| 700 | 1 | |a Heck, Albert J.R. |0 (orcid)0000-0002-2405-4404 |4 aut | |
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