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ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.
Kaplonek, Paulina; Cizmeci, Deniz; Kwatra, Gaurav; Izu, Alane; Lee, Jessica Shih-Lu; Bertera, Harry L; Fischinger, Stephanie; Mann, Colin; Amanat, Fatima; Wang, Wenjun; Koen, Anthonet L; Fairlie, Lee; Cutland, Clare L; Ahmed, Khatija; Dheda, Keertan; Barnabas, Shaun L; Bhorat, Qasim Ebrahim; Briner, Carmen; Krammer, Florian; Saphire, Erica Ollman; Gilbert, Sarah C; Lambe, Teresa; Pollard, Andrew J; Nunes, Marta; Wuhrer, Manfred; Lauffenburger, Douglas A; Madhi, Shabir A; Alter, Galit.
Affiliation
  • Kaplonek P; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Cizmeci D; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Kwatra G; South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Izu A; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, University of the Witwatersrand, Johannesburg, South Africa.
  • Lee JS; African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Bertera HL; South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Fischinger S; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, University of the Witwatersrand, Johannesburg, South Africa.
  • Mann C; African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Amanat F; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Wang W; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Koen AL; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Fairlie L; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Cutland CL; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Ahmed K; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.
  • Dheda K; South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Barnabas SL; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, University of the Witwatersrand, Johannesburg, South Africa.
  • Bhorat QE; African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Briner C; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Krammer F; African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Saphire EO; Setshaba Research Centre, Tshwane, South Africa.
  • Gilbert SC; Division of Pulmonology, Groote Schuur Hospital and the University of Cape Town, Cape Town, South Africa.
  • Lambe T; Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.
  • Pollard AJ; Family Centre for Research With Ubuntu, Department of Paediatrics, University of Stellenbosch, Cape Town, South Africa.
  • Nunes M; Soweto Clinical Trials Centre, Soweto, South Africa.
  • Wuhrer M; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Lauffenburger DA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Madhi SA; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Alter G; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nat Immunol ; 24(7): 1161-1172, 2023 07.
Article in En | MEDLINE | ID: mdl-37322179
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.
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Full text: 1 Database: MEDLINE Main subject: Vaccines / COVID-19 Type of study: Clinical_trials Limits: Humans Language: En Journal: Nat Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2023 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Vaccines / COVID-19 Type of study: Clinical_trials Limits: Humans Language: En Journal: Nat Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2023 Type: Article Affiliation country: United States