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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, Sian E
; 
Newby, Maddy L
; 
Chapple, Iain
; 
Dietrich, Thomas
; ... show 10 more
Authors
Lamerton, Rachel E
 Marcial-Juarez, Edith
 Faustini, Sian E
 Perez-Toledo, Marisol
 Goodall, Margaret
 Jossi, Sian 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
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2022-07-04
Submitted date
Subjects
complement
 COVID-19
 SARS-CoV-2
 vaccine
 antibodies
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Abstract
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.
Citation
Lamerton RE, Marcial-Juarez E, Faustini SE, Perez-Toledo M, Goodall M, Jossi SE, Newby ML, Chapple I, Dietrich T, Veenith T, Shields AM, Harper L, Henderson IR, Rayes J, Wraith DC, Watson SP, Crispin M, Drayson MT, Richter AG and Cunningham AF (2022) SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation. Front. Immunol. 13:838780. doi: 10.3389/fimmu.2022.838780
Publisher
Frontiers Media SA
Journal
Frontiers in Immunology
Research Unit
URI
https://wlv.openrepository.com/handle/2436/626338
DOI
10.3389/fimmu.2022.838780
PubMed ID
35860286 (pubmed)
PubMed Central ID
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Additional Links
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.838780/full
Type
Journal article
Language
en
Description
© 2022 The Authors. Published by Frontiers Media SA. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3389/fimmu.2022.838780
Series/Report no.
ISSN
1664-3224
EISSN
1664-3224
ISBN
ISMN
Gov't Doc #
Sponsors
This work was supported by the Wellcome Trust Mechanisms of Inflammatory Disease (MIDAS) PhD Programme [grant number 222389/Z/21/Z, part of 108871/B/15/Z] to RL; The Royal Society Newton International Fellowship [grant number NIF\R1\192061] to E.M.J and AC; a British Heart Foundation Intermediate Fellowship [grant number FS/IBSRF/20/25039] to JR; The University of Southampton Coronavirus Response Fund to MC and Medical Research Council [grant number MR/W010011/1] to LH, AR and AC.
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Licence for published version: Creative Commons Attribution 4.0 International
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