The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees.

Julie Van Coillie ,Theo Rispens ,Alessandro Torre ,Michiel Schinkel ,Tonći Šuštić ,Marco Schiuma ,Giovanna Bestetti ,Thijs L J Van Osch ,Gestur Vidarsson ,Mario Corbellino ,Lonneke A Vught Van ,Willianne Hoepel ,Diederik Beek Van De ,Jan Nouta ,Hanna B Lunding ,Brent Appelman ,Hung Jen Chen ,Matthijs C Brouwer ,David T.p Buis ,Justin Brabander De ,Ayesha H.a Lavell ,Carsten Kern ,Inga Künsting ,Emily Martin ,Edgar J.g Peters ,Sabine E Olie ,Manfred Wuhrer ,Spinello Antinori ,Marc Ehlers ,Tamás Pongrácz ,Niels Mourik Van ,Yvo M Smulders ,Sofie Keijzer ,Marit J Gils Van ,Chiara E Geyer ,Lonneke A Van Vught ,Vera Von Kopylow ,Nora Chekrouni ,Wenjun Wang ,Tom D Y Reijnders ,A Lupo ,R P Minnaar ,Marleen A Slim ,Anne Sophie Lixenfeld ,Marije Bomers ,Mads Delbo Larsen ,Alexander P.j Vlaar ,Niels Van Mourik ,C Ellen Van Der Schoot ,Tobias Graf ,Federica Linty ,Jana Sophia Buhre ,Alex R Schuurman ,Menno D Jong De ,Maurice Steenhuis ,Jeroen Den Dunnen ,Jonne J Sikkens ,Laura Milazzo ,Menno P.j De Winther ,Selina Lehrian ,Remco Visser ,Alice Covizzi ,Johann Rahmöller ,Cinzia Bassoli ,Joost W Wiersinga

doi:10.1016/j.ebiom.2022.104408

Abstract

Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses. Blood from vaccinees during the first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) was used to study anti-S IgG1 Fc glycoprofiles. Responsiveness of alveolar-like macrophages to produce proinflammatory cytokines in presence of sera and antigen was tested. Antigen-specific B cells were characterized and glycosyltransferase levels were investigated by Fluorescence-Activated Cell Sorting (FACS). Initial transient afucosylated anti-S IgG1 responses were found in naive vaccinees, but not in antigen-experienced ones. All vaccinees had increased 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 expression 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. Here, we show that BNT162b2 mRNA vaccination induces transient afucosylated anti-S IgG1 responses in naive individuals. This observation warrants further studies to elucidate the clinical context in which potent afucosylated responses would be preferred. LSBR1721, 1908; ZonMW10430012010021, 09150161910033, 10430012010008; DFG398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.

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