Antibody-dependent cellular cytotoxicity against SARS-CoV-2 Omicron sub-lineages is reduced in convalescent sera regardless of infecting variant

Simone I Richardson; Prudence Kgagudi; Nelia P Manamela; Haajira Kaldine; Elizabeth M Venter; Thanusha Pillay; Bronwen E Lambson; Mieke A van der Mescht; Tandile Hermanus; Sashkia R Balla; Zelda de Beer; Talita R de Villiers; Annie Bodenstein; Gretha van den Berg; Marizane du Pisanie; Wendy A Burgers; Ntobeko A B Ntusi; Fareed Abdullah; Veronica Ueckermann; Theresa M Rossouw; Michael T Boswell; Penny L Moore

doi:10.1016/j.xcrm.2022.100910

Antibody-dependent cellular cytotoxicity against SARS-CoV-2 Omicron sub-lineages is reduced in convalescent sera regardless of infecting variant

Cell Rep Med. 2023 Jan 17;4(1):100910. doi: 10.1016/j.xcrm.2022.100910. Epub 2022 Dec 22.

Authors

Simone I Richardson¹, Prudence Kgagudi¹, Nelia P Manamela¹, Haajira Kaldine¹, Elizabeth M Venter¹, Thanusha Pillay¹, Bronwen E Lambson¹, Mieke A van der Mescht², Tandile Hermanus¹, Sashkia R Balla¹, Zelda de Beer³, Talita R de Villiers³, Annie Bodenstein³, Gretha van den Berg³, Marizane du Pisanie⁴, Wendy A Burgers⁵, Ntobeko A B Ntusi⁶, Fareed Abdullah⁷, Veronica Ueckermann⁴, Theresa M Rossouw², Michael T Boswell⁴, Penny L Moore⁸

Affiliations

¹ National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa; South African Medical Research Council Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
² Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
³ Tshwane District Hospital, Pretoria, South Africa.
⁴ Division for Infectious Diseases, Department of Internal Medicine, Steve Biko Academic Hospital and University of Pretoria, Pretoria, South Africa.
⁵ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Division of Medical Virology, Department of Pathology; University of Cape Town, Cape Town, South Africa; Wellcome Centre for Infectious Disease Research in Africa, University of Cape Town, Cape Town, South Africa.
⁶ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa; Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁷ Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Division for Infectious Diseases, Department of Internal Medicine, Steve Biko Academic Hospital and University of Pretoria, Pretoria, South Africa.
⁸ National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa; South African Medical Research Council Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa. Electronic address: pennym@nicd.ac.za.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.4 and BA.5 variants caused major waves of infections. Here, we assess the sensitivity of BA.4 to binding, neutralization, and antibody-dependent cellular cytotoxicity (ADCC) potential, measured by FcγRIIIa signaling, in convalescent donors infected with four previous variants of SARS-CoV-2, as well as in post-vaccination breakthrough infections (BTIs) caused by Delta or BA.1. We confirm that BA.4 shows high-level neutralization resistance regardless of the infecting variant. However, BTIs retain activity against BA.4, albeit at reduced titers. BA.4 sensitivity to ADCC is reduced compared with other variants but with smaller fold losses compared with neutralization and similar patterns of cross-reactivity. Overall, the high neutralization resistance of BA.4, even to antibodies from BA.1 infection, provides an immunological mechanism for the rapid spread of BA.4 immediately after a BA.1-dominated wave. Furthermore, although ADCC potential against BA.4 is reduced, residual activity may contribute to observed protection from severe disease.

Keywords: COVID-19; Fc effector function; Omicron BA.4; SARS-CoV-2; VOC; antibody-dependent cellular cytotoxicity; breakthrough infection; neutralization.

Publication types

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

MeSH terms

Antibodies
Antibody-Dependent Cell Cytotoxicity*
Breakthrough Infections
COVID-19 / immunology
COVID-19 / therapy
COVID-19 Serotherapy*
Humans
SARS-CoV-2* / immunology

Substances

Antibodies