Anti-SARS-Cov-2 S-RBD IgG Formed after BNT162b2 Vaccination Can Bind C1q and Activate Complement
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Abstract
Background. The ability of vaccine-induced antibodies to bind C1q could affect pathogen neutralization. In this study, we investigated C1q binding and subsequent complement activation by anti-spike (S) protein receptor-binding domain (RBD) specific antibodies produced following vaccination with either the mRNA vaccine BNT162b2 or the inactivated vaccine BBIBP-CorV. Methods. Serum samples were collected in the period of July 2021-March 2022. Participants’ demographic data, type of vaccine, date of vaccination, as well as adverse effects of the vaccine were recorded. The serum samples were incubated with S protein RBD-coated plates. Levels of human IgG, IgA, IgM, C1q, and mannose-binding lectin (MBL) that were bound to the plate, as well as formed C3d, and C5b-9 were compared between different groups of participants. Results. A total of 151 samples were collected from vaccinated ( n = 116 ) and nonvaccinated ( n = 35 ) participants. Participants who received either one or two doses of BNT162b2 formed higher levels of anti-RBD IgG and IgA than participants who received BBIBP-CorV. The anti-RBD IgG formed following either vaccine bound C1q, but significantly more C1q binding was observed in participants who received BNT162b2. Subsequently, C5b-9 formation was significantly higher in participants who received BNT162b2, while no significant difference in C5b-9 formation was found between the nonvaccinated and BBIBP-CorV groups. The formation of C5b-9 was strongly correlated to C1q binding and not to MBL binding, additionally, the ratio of formed C5b-9/bound C1q was significantly higher in the BNT162b2 group. Conclusion. Anti-RBD IgG formed following vaccination can bind C1q with subsequent complement activation, and the degree of terminal complement pathway activation differed between vaccines, which could play a role in the protection offered by COVID-19 vaccines. Further investigation into the correlation between vaccine protection and vaccine-induced antibodies’ ability to activate complement is required.
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SciScore for 10.1101/2022.04.24.489298: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Sample collection: Samples were collected in plain blood collection tubes with a gel separator, then immediately preserved at 4°C and allowed to clot for a maximum of 2 hours.
IRB: Ethical approval: The study protocol was approved by the Institutional Review Board (IRB) at UJ (Ref. No. 68/2021).
Consent: A written and signed informed consent was obtained from all participants who agreed to participate following a full explanation of the study objectives.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources For IgG and IgM measurement, plates were incubated with either … SciScore for 10.1101/2022.04.24.489298: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Sample collection: Samples were collected in plain blood collection tubes with a gel separator, then immediately preserved at 4°C and allowed to clot for a maximum of 2 hours.
IRB: Ethical approval: The study protocol was approved by the Institutional Review Board (IRB) at UJ (Ref. No. 68/2021).
Consent: A written and signed informed consent was obtained from all participants who agreed to participate following a full explanation of the study objectives.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources For IgG and IgM measurement, plates were incubated with either horseradish peroxidase (HRP)-conjugated rabbit anti-human IgG polyclonal antibodies (Abcam), or HRP-conjugated rabbit anti-human IgM polyclonal antibodies (Novus) respectively, both at a concentration of 1:2000 in blocking buffer at 4° C overnight. anti-human IgGsuggested: (Abcam Cat# 2000-1, RRID:AB_765103)anti-human IgMsuggested: NoneWhile for C1q and C5b-9 measurement, the wells were washed three times with PBST, then incubated with either rabbit anti-human C1q polyclonal antibodies (MyBioSource) or mouse anti-human C5b-9 monoclonal antibodies (Novus), respectively, at a concentration of 1:500 in blocking buffer at 4° C overnight. anti-human C1qsuggested: Noneanti-human C5b-9suggested: NoneThe next day, the wells were washed three times with PBST, then incubated with the following secondary antibodies for 3 hours at room temperature; HRP-conjugated goat anti-rabbit polyclonal antibodies (Novex Life Technologies) for C1q, and HRP-conjugated goat anti-mouse polyclonal antibodies (Abcam) for C5b-9. anti-rabbitsuggested: NoneC1qsuggested: Noneanti-mouse polyclonal antibodiessuggested: NoneC5b-9suggested: NoneSoftware and Algorithms Sentences Resources The image files were analyzed using Fiji/ImageJ [16]. Fiji/ImageJsuggested: NoneData Analysis: Data generated was organized in Microsoft Excel, and statistical analysis was carried out using GraphPad prism 8 software for analysis. Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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