SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation
Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathologi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.838780/full |
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| author | Rachel E. Lamerton Rachel E. Lamerton Edith Marcial-Juarez Sian E. Faustini Marisol Perez-Toledo Margaret Goodall Siân E. Jossi Maddy L. Newby Iain Chapple Thomas Dietrich Tonny Veenith Adrian M. Shields Lorraine Harper Ian R. Henderson Julie Rayes David C. Wraith Steve P. Watson Max Crispin Mark T. Drayson Alex G. Richter Adam F. Cunningham |
| author_facet | Rachel E. Lamerton Rachel E. Lamerton Edith Marcial-Juarez Sian E. Faustini Marisol Perez-Toledo Margaret Goodall Siân E. Jossi Maddy L. Newby Iain Chapple Thomas Dietrich Tonny Veenith Adrian M. Shields Lorraine Harper Ian R. Henderson Julie Rayes David C. Wraith Steve P. Watson Max Crispin Mark T. Drayson Alex G. Richter Adam F. Cunningham |
| author_sort | Rachel E. Lamerton |
| collection | DOAJ |
| description | Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of antibodies to SARS-CoV-2 from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the subject group from whom the sera were obtained. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending the disease status of the subject and on the specific antigen targeted. |
| first_indexed | 2024-04-13T14:02:39Z |
| format | Article |
| id | doaj.art-e96e183f4c0140d195866a01fcba3220 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T14:02:39Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e96e183f4c0140d195866a01fcba32202022-12-22T02:44:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.838780838780SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement ActivationRachel E. Lamerton0Rachel E. Lamerton1Edith Marcial-Juarez2Sian E. Faustini3Marisol Perez-Toledo4Margaret Goodall5Siân E. Jossi6Maddy L. Newby7Iain Chapple8Thomas Dietrich9Tonny Veenith10Adrian M. Shields11Lorraine Harper12Ian R. Henderson13Julie Rayes14David C. Wraith15Steve P. Watson16Max Crispin17Mark T. Drayson18Alex G. Richter19Adam F. Cunningham20Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomSchool of Biological Sciences, University of Southampton, Southampton, United KingdomPeriodontal Research Group, School of Dentistry, Institute of Clinical Sciences, University of Birmingham, and Birmingham Community Healthcare National Health Service Trust, Birmingham, United KingdomPeriodontal Research Group, School of Dentistry, Institute of Clinical Sciences, University of Birmingham, and Birmingham Community Healthcare National Health Service Trust, Birmingham, United KingdomDepartment of Critical Care Medicine, University Hospitals Birmingham National Health Service (NHS) Trust, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Applied Health Research, University of Birmingham, Birmingham, United KingdomInstitute for Molecular Bioscience, University of Queensland, St Lucia, QLD, AustraliaInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biological Sciences, University of Southampton, Southampton, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomAntibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of antibodies to SARS-CoV-2 from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the subject group from whom the sera were obtained. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending the disease status of the subject and on the specific antigen targeted.https://www.frontiersin.org/articles/10.3389/fimmu.2022.838780/fullcomplementCOVID-19SARS-CoV-2vaccineantibodies |
| spellingShingle | Rachel E. Lamerton Rachel E. Lamerton Edith Marcial-Juarez Sian E. Faustini Marisol Perez-Toledo Margaret Goodall Siân E. Jossi Maddy L. Newby Iain Chapple Thomas Dietrich Tonny Veenith Adrian M. Shields Lorraine Harper Ian R. Henderson Julie Rayes David C. Wraith Steve P. Watson Max Crispin Mark T. Drayson Alex G. Richter Adam F. Cunningham SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation Frontiers in Immunology complement COVID-19 SARS-CoV-2 vaccine antibodies |
| title | SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation |
| title_full | SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation |
| title_fullStr | SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation |
| title_full_unstemmed | SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation |
| title_short | SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation |
| title_sort | sars cov 2 spike and nucleoprotein specific antibodies induced after vaccination or infection promote classical complement activation |
| topic | complement COVID-19 SARS-CoV-2 vaccine antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.838780/full |
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