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 Saphire; Sarah C Gilbert; Teresa Lambe; Andrew J Pollard; Marta Nunes; Manfred Wuhrer; Douglas A Lauffenburger; Shabir A Madhi; Galit Alter

doi:10.1038/s41590-023-01513-1

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

Nat Immunol. 2023 Jul;24(7):1161-1172. doi: 10.1038/s41590-023-01513-1. Epub 2023 Jun 15.

Authors

Paulina Kaplonek^#¹, Deniz Cizmeci^#¹, Gaurav Kwatra^#^{2

3

4}, Alane Izu^{2

3

4}, Jessica Shih-Lu Lee¹, Harry L Bertera¹, Stephanie Fischinger¹, Colin Mann⁵, Fatima Amanat⁶, Wenjun Wang⁷, Anthonet L Koen^{2

3}, Lee Fairlie^{4

8}, Clare L Cutland⁴, Khatija Ahmed⁹, Keertan Dheda^{10

11}, Shaun L Barnabas¹², Qasim Ebrahim Bhorat¹³, Carmen Briner¹⁴, Florian Krammer⁶, Erica Ollman Saphire⁵, Sarah C Gilbert¹⁵, Teresa Lambe¹⁶, Andrew J Pollard¹⁶, Marta Nunes^{2

3

4}, Manfred Wuhrer⁷, Douglas A Lauffenburger¹⁷, Shabir A Madhi^#^{18

19

20}, Galit Alter^#²¹

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
² South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ 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.
⁴ African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA.
⁶ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷ Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.
⁸ Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ Setshaba Research Centre, Tshwane, South Africa.
¹⁰ Division of Pulmonology, Groote Schuur Hospital and the University of Cape Town, Cape Town, South Africa.
¹¹ Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.
¹² Family Centre for Research With Ubuntu, Department of Paediatrics, University of Stellenbosch, Cape Town, South Africa.
¹³ Soweto Clinical Trials Centre, Soweto, South Africa.
¹⁴ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁵ Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁶ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹⁷ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁸ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. shabir.madhi@wits.ac.za.
¹⁹ 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. shabir.madhi@wits.ac.za.
²⁰ African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. shabir.madhi@wits.ac.za.
²¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. galit.alter@gmail.com.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines / adverse effects
COVID-19* / prevention & control
ChAdOx1 nCoV-19
Humans
Immunoglobulin G
Receptors, Fc / genetics
SARS-CoV-2
Vaccination
Vaccines*

Substances

ChAdOx1 nCoV-19
COVID-19 Vaccines
Vaccines
Antibodies, Viral
Immunoglobulin G
Receptors, Fc
Antibodies, Neutralizing

Abstract

Publication types

MeSH terms

Substances

Grants and funding