Anti-SARS-Cov-2 S-RBD IgG formed after BNT162b2 vaccination can bind C1q and activate complement

Abstract

IntroductionActivation of the classical complement pathway through C1q binding to immunoglobulins (Ig) contributes to pathogen neutralization, thus, the ability of Ig produced after vaccination to bind C1q could affect vaccine efficacy. 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. MethodsSerum samples were collected in the period 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, IgM, and C1q, that were bound to the plate, as well as formed C5b-9, were compared between different groups of participants. ResultsA total of 151 samples were collected from vaccinated (n=116) and non-vaccinated (n=35) participants. Participants who received either one or two doses of BNT162b2 formed higher levels of anti-RBD IgG 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 non-vaccinated and BBIBP-CorV groups. Formation of C5b-9 was strongly correlated to C1q binding, additionally, the ratio of formed C5b-9/ bound C1q was significantly higher in the BNT162b2 group. ConclusionAnti-RBD IgG formed following vaccination can bind C1q with subsequent complement activation, the degree of terminal complement pathway activation differed between vaccines, which could play a role in in the protection offered by COVID-19 vaccines. Further investigation into the correlation between vaccine protection and the ability of vaccine generated antibodies to activate complement is required.