We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG reactions. Methods Blood from vaccinees during the first vaccination wave was collected. levels were investigated by Fluorescence-Activated Cell Sorting (FACS). Findings Initial transient afucosylated anti-S IgG1 reactions were found in naive vaccinees, but not in antigen-experienced ones. All vaccinees experienced improved galactosylated and sialylated anti-S IgG1. Both naive and antigen-experienced vaccinees showed relatively low macrophage activation potential, as expected, due to the low antibody levels for naive individuals with afucosylated IgG1, and low afucosylation levels for antigen-experienced individuals with high levels of anti-S. Afucosylation levels correlated with FUT8 manifestation in antigen-specific plasma cells in naive individuals. Interestingly, low fucosylation of anti-S IgG1 upon seroconversion correlated with high anti-S IgG levels after the second dose. Interpretation Here, we display that BNT162b2 mRNA vaccination induces transient afucosylated anti-S IgG1 reactions in naive individuals. This observation warrants further studies to elucidate the medical context in which potent afucosylated reactions would be desired. Funding LSBR1721, 1908; ZonMW10430012010021, 09150161910033, 10430012010008; DFG398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815. Keywords: mRNA Vaccine, Antibodies, Glycosylation, Fucosylation, COVID-19 Study in context Evidence before this study Antibodies are crucial for protecting immunity, which depends on both the amount of IgG and on its Fc antigens indicated on erythrocytes22 and to foreign proteins of enveloped viruses, including human being immunodeficiency disease (HIV),23 dengue TCS PIM-1 4a (SMI-4a) disease,24 and SARS-CoV-2.2,3 The common characteristic of such responses is that the related pathogen-specific antigens are generally expressed within the host cell membrane, unlike TCS PIM-1 4a (SMI-4a) most foreign antigens. Afucosylated IgG has an enhanced binding of up to 40 instances to FcRIII in comparison to its fucosylated counterpart. This results in improved cytokine production and cellular reactions, such as Ab-dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC). These reactions by far surpass the 40 instances enhancement of binding affinity of afucosylated IgG to FcRIII, presumably due to improved avidity between IgG-opsonized focuses on and FcRIII-expressing effector cells.5, 6, 7,25 Intriguingly, pathogen-specific afucosylated IgG1 responses can be favourable, such as the protection seen in TCS PIM-1 4a (SMI-4a) malaria22 and HIV,23 but can in turn cause massive inflammation via FcRIII-mediated pathologies in individuals with severe dengue fever,24 and has been shown to correlate with severe COVID-19.1,3,5,26 Full enhancement of this inflammatory response in COVID-19 also requires activation of various TLR members, contributing to triggering of a pro-inflammatory environment,27 including cytokine release such as IL-6, which is also only found systemically elevated in individuals with severe COVID infections.1,2 In contrast, non-enveloped viruses, bacteria, and soluble protein-subunit vaccines, all lacking the host cell membrane context, induce virtually no afucosylated IgG responses. These include recombinant hepatitis B disease (HBV) and macrophage activation assay. Methods This study was designed to investigate the effect of the BNT162b2 BioNTech/Pfizer mRNA vaccine on anti-Spike IgG1 Fc glycosylation and Personal computer subsets. We acquired serum, plasma and/or PBMC samples from vaccinated participants from 1) healthcare works in the Amsterdam UMC, The Netherlands (n?=?39), 2) The Fatebenefratelli-Sacco Infectious Diseases Physicians Group (n?=?9), 3) the University or college Medical Center of Schleswig-Holstein, Lbeck, Germany (n?=?40), and 4) the Dutch blood bank Sanquin, the Netherlands. The discrimination between vaccinated SARS-CoV-2 naive and antigen-experienced participants was made by serology (anti-Spike and anti-Nucleocapsid IgG) and positive PCR-tests before vaccination. No additional selection criteria were used and participants were selected at random. Vaccination study cohorts and control individuals Cohort 1. Amsterdam UMC cohort Subjects were part of the S3 cohort study (S3 cohort; NL 73478.029.20, Netherlands Trial Register NL8645), a prospective serologic monitoring cohort study among hospital healthcare workers in the Amsterdam University or college Medical Center (Amsterdam UMC). Between TCS PIM-1 4a (SMI-4a) January and March 2021, 39 cohort participants received their first dose of BioNTech/Pfizer mRNA vaccine (BNT162b2, 30?g) (Table?S2). A second dose was given approximately 21 days after the 1st dose. Samples were acquired directly before and 3, 7, 10 and 14 days after the 1st dose, and directly before and 3, 7, 10, 14, 21 and 28 days after the second dose (Table?S2). Cohort 2. The Fatebenefratelli-Sacco Infectious Diseases Physicians Group Nine healthcare workers in the Luigi Sacco Infectious Diseases Hospital, Milano, Italy were immunized with Mouse monoclonal to HPC4. HPC4 is a vitamin Kdependent serine protease that regulates blood coagluation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.
HPC4 Tag antibody can recognize Cterminal, internal, and Nterminal HPC4 Tagged proteins. BioNTech/Pfizer mRNA vaccine (BNT162b2, 30?g) and received a 2nd dose 21 days after the 1st dose. Blood samples were acquired directly before the 1st dose, and twice a week for six weeks from December 2020 to February 2021 (Table?S3). Cohort 3. Lbeck cohort Forty subjects were recruited in the University Medical Center of Schleswig-Holstein, Lbeck, Germany from December 2020 (including samples (participants 1C22; Table?S4) described in Lixenfeld et?al.29): 1) 32 individuals immunized with the BioNTech/Pfizer vaccine BNT162b2 (30?g) without or with known SARS-CoV-2 illness history (19 of these 32 individuals (analysed in Fig.?S1) received the 2nd dose between day time 32 and 37 after the 1st) and 2) and 8 unvaccinated individuals without SARS-CoV-2 illness history as negative control (Table?S4). Cohort 4. Convalescent plasma donors.