ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19

Paulina Kaplonek, Deniz Cizmeci, Gaurav Kwatra, Alane Izu, Jessica Shih Lu Lee, Harry L. Bertera, Stephanie Fischinger, Colin Mann, Fatima Amanat, Wenjun Wang, Anthonet L. Koen, Lee Fairlie, Clare L. Cutland, Khatija Ahmed, Keertan Dheda, Shaun L. Barnabas, Qasim Ebrahim Bhorat, Carmen Briner, Florian Krammer, Erica Ollman SaphireSarah C. Gilbert, Teresa Lambe, Andrew J. Pollard, Marta Nunes, Manfred Wuhrer, Douglas A. Lauffenburger, Shabir A. Madhi, Galit Alter

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed in immunoglobulin (Ig)G1-binding antibody titers; however, the vaccine induced different Fc-receptor-binding antibodies across groups. Vaccinees who resisted COVID-19 exclusively mounted FcγR3B-binding antibodies. In contrast, enhanced IgA and IgG3, linked to enriched FcγR2B binding, was observed in individuals who experienced breakthrough. Antibodies unable to bind to FcγR3B led to immune complex clearance and resulted in inflammatory cascades. Differential antibody binding to FcγR3B was linked to Fc-glycosylation differences in SARS-CoV-2-specific antibodies. These data potentially point to specific FcγR3B-mediated antibody functional profiles as critical markers of immunity against COVID-19.

Original languageEnglish
Pages (from-to)1161-1172
Number of pages12
JournalNature Immunology
Volume24
Issue number7
DOIs
StatePublished - Jul 2023

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