SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity

Simone I Richardson; Nelia P Manamela; Boitumelo M Motsoeneng; Haajira Kaldine; Frances Ayres; Zanele Makhado; Mathilda Mennen; Sango Skelem; Noleen Williams; Nancy J Sullivan; John Misasi; Glenda G Gray; Linda-Gail Bekker; Veronica Ueckermann; Theresa M Rossouw; Michael T Boswell; Ntobeko A B Ntusi; Wendy A Burgers; Penny L Moore

doi:10.1016/j.xcrm.2022.100510

SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity

Cell Rep Med. 2022 Jan 17;3(2):100510. doi: 10.1016/j.xcrm.2022.100510. eCollection 2022 Feb 15.

Authors

Simone I Richardson^{1

2}, Nelia P Manamela^{1

2}, Boitumelo M Motsoeneng^{1

2}, Haajira Kaldine^{1

2}, Frances Ayres^{1

2}, Zanele Makhado^{1

2}, Mathilda Mennen³, Sango Skelem³, Noleen Williams³, Nancy J Sullivan⁴, John Misasi⁴, Glenda G Gray⁵, Linda-Gail Bekker⁶, Veronica Ueckermann⁷, Theresa M Rossouw⁸, Michael T Boswell⁷, Ntobeko A B Ntusi^{9

3

10

11}, Wendy A Burgers^{9

12

11}, Penny L Moore^{1

2

9

13}

Affiliations

¹ National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg 2131, South Africa.
² SA MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg 2001, South Africa.
³ Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Cape Town 7701, South Africa.
⁴ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ The South African Medical Research Council, Tygerberg 7505, South Africa.
⁶ The Desmond Tutu HIV Centre, University of Cape Town, Cape Town 7705, South Africa.
⁷ Division for Infectious Diseases, Department of Internal Medicine, Steve Biko Academic Hospital and University of Pretoria, Pretoria 0002, South Africa.
⁸ Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa.
⁹ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7701, South Africa.
¹⁰ Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town 7701, South Africa.
¹¹ Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town 7701, South Africa.
¹² Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7701, South Africa.
¹³ Centre for the AIDS Programme of Research in South Africa, Durban 4013, South Africa.

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with improved disease outcome and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta and Delta infection trigger responses with significantly improved Fc cross-reactivity against global VOCs compared with D614G-infected or Ad26.COV2.S-vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence affects Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses.

Keywords: Ad26.COV2.S; Beta; Delta; Fc effector function; SARS-CoV-2; variant of concern.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ad26COVS1 / immunology
Ad26COVS1 / therapeutic use
Adult
Aged
Antibodies, Neutralizing / immunology*
Antibodies, Viral / immunology*
COVID-19 / blood
COVID-19 / immunology*
COVID-19 / prevention & control
COVID-19 / virology
Cohort Studies
Cross Reactions
Female
HEK293 Cells
Humans
Immunoglobulin Fc Fragments / immunology*
Jurkat Cells
Male
Middle Aged
Neutralization Tests
Protein Binding
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / immunology
THP-1 Cells
Treatment Outcome
Vaccination / methods

Substances

Ad26COVS1
Antibodies, Neutralizing
Antibodies, Viral
Immunoglobulin Fc Fragments
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

MRC_/Medical Research Council/United Kingdom