@article{Richardson2023,
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 Fc$\gamma$RIIIa 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.},
author = {Richardson, Simone I and Kgagudi, Prudence and Manamela, Nelia P and Kaldine, Haajira and Venter, Elizabeth M and Pillay, Thanusha and Lambson, Bronwen E and van der Mescht, Mieke A and Hermanus, Tandile and Balla, Sashkia R and de Beer, Zelda and de Villiers, Talita R and Bodenstein, Annie and van den Berg, Gretha and du Pisanie, Marizane and Burgers, Wendy A and Ntusi, Ntobeko A B and Abdullah, Fareed and Ueckermann, Veronica and Rossouw, Theresa M and Boswell, Michael T and Moore, Penny L},
doi = {10.1016/j.xcrm.2022.100910},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Richardson et al. - 2023 - Antibody-dependent cellular cytotoxicity against SARS-CoV-2 Omicron sub-lineages is reduced in convalescent s.pdf:pdf},
issn = {26663791},
journal = {Cell Reports Medicine},
keywords = {COVID-19,Fc effector function,OA,Omicron BA.4,SARS-CoV-2,VOC,antibody-dependent cellular cytotoxicity,breakthrough infection,fund{\_}not{\_}ack,neutralization,original},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {jan},
number = {1},
pages = {100910},
publisher = {Cell Press},
title = {{Antibody-dependent cellular cytotoxicity against SARS-CoV-2 Omicron sub-lineages is reduced in convalescent sera regardless of infecting variant}},
url = {http://www.cell.com/article/S266637912200489X/fulltext http://www.cell.com/article/S266637912200489X/abstract https://www.cell.com/cell-reports-medicine/abstract/S2666-3791(22)00489-X},
volume = {4},
year = {2023}
}

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Here, we assess the sensitivity of BA.4 to binding, neutralization, and antibody-dependent cellular cytotoxicity (ADCC) potential, measured by Fc$γ$RIIIa 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. 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