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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...

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Autores principales: Lamerton, Rachel E., Marcial-Juarez, Edith, Faustini, Sian E., Perez-Toledo, Marisol, Goodall, Margaret, Jossi, Siân E., Newby, Maddy L., Chapple, Iain, Dietrich, Thomas, Veenith, Tonny, Shields, Adrian M., Harper, Lorraine, Henderson, Ian R., Rayes, Julie, Wraith, David C., Watson, Steve P., Crispin, Max, Drayson, Mark T., Richter, Alex G., Cunningham, Adam F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289266/
https://www.ncbi.nlm.nih.gov/pubmed/35860286
http://dx.doi.org/10.3389/fimmu.2022.838780
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author Lamerton, Rachel E.
Marcial-Juarez, Edith
Faustini, Sian E.
Perez-Toledo, Marisol
Goodall, Margaret
Jossi, Siân E.
Newby, Maddy L.
Chapple, Iain
Dietrich, Thomas
Veenith, Tonny
Shields, Adrian M.
Harper, Lorraine
Henderson, Ian R.
Rayes, Julie
Wraith, David C.
Watson, Steve P.
Crispin, Max
Drayson, Mark T.
Richter, Alex G.
Cunningham, Adam F.
author_facet Lamerton, Rachel E.
Marcial-Juarez, Edith
Faustini, Sian E.
Perez-Toledo, Marisol
Goodall, Margaret
Jossi, Siân E.
Newby, Maddy L.
Chapple, Iain
Dietrich, Thomas
Veenith, Tonny
Shields, Adrian M.
Harper, Lorraine
Henderson, Ian R.
Rayes, Julie
Wraith, David C.
Watson, Steve P.
Crispin, Max
Drayson, Mark T.
Richter, Alex G.
Cunningham, Adam F.
author_sort Lamerton, Rachel E.
collection PubMed
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.
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spelling pubmed-92892662022-07-19 SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation Lamerton, Rachel E. Marcial-Juarez, Edith Faustini, Sian E. Perez-Toledo, Marisol Goodall, Margaret Jossi, Siân E. Newby, Maddy L. Chapple, Iain Dietrich, Thomas Veenith, Tonny Shields, Adrian M. Harper, Lorraine Henderson, Ian R. Rayes, Julie Wraith, David C. Watson, Steve P. Crispin, Max Drayson, Mark T. Richter, Alex G. Cunningham, Adam F. Front Immunol Immunology 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. Frontiers Media S.A. 2022-07-04 /pmc/articles/PMC9289266/ /pubmed/35860286 http://dx.doi.org/10.3389/fimmu.2022.838780 Text en Copyright © 2022 Lamerton, Marcial-Juarez, Faustini, Perez-Toledo, Goodall, Jossi, Newby, Chapple, Dietrich, Veenith, Shields, Harper, Henderson, Rayes, Wraith, Watson, Crispin, Drayson, Richter and Cunningham https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lamerton, Rachel E.
Marcial-Juarez, Edith
Faustini, Sian E.
Perez-Toledo, Marisol
Goodall, Margaret
Jossi, Siân E.
Newby, Maddy L.
Chapple, Iain
Dietrich, Thomas
Veenith, Tonny
Shields, Adrian M.
Harper, Lorraine
Henderson, Ian R.
Rayes, Julie
Wraith, David C.
Watson, Steve P.
Crispin, Max
Drayson, Mark T.
Richter, Alex G.
Cunningham, Adam F.
SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289266/
https://www.ncbi.nlm.nih.gov/pubmed/35860286
http://dx.doi.org/10.3389/fimmu.2022.838780
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