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

被引：10
作者：
Richardson, Simone I. [1 ,2 ]
Kgagudi, Prudence [1 ,2 ]
Manamela, Nelia P. [1 ,2 ]
Kaldine, Haajira [1 ,2 ]
Venter, Elizabeth M. [1 ,2 ]
Pillay, Thanusha [1 ,2 ]
Lambson, Bronwen E. [1 ,2 ]
van der Mescht, Mieke A. [3 ]
Hermanus, Tandile [1 ,2 ]
Balla, Sashkia R. [1 ,2 ]
de Beer, Zelda [4 ]
de Villiers, Talita R. [4 ]
Bodenstein, Annie [4 ]
van den Berg, Gretha [4 ]
du Pisanie, Marizane [5 ,6 ]
Burgers, Wendy A. [7 ,8 ,9 ]
Ntusi, Ntobeko A. B. [7 ,10 ,11 ,12 ,13 ]
Abdullah, Fareed [3 ,5 ,6 ]
Ueckermann, Veronica [5 ,6 ]
Rossouw, Theresa M. [3 ]
Boswell, Michael T. [1 ,2 ,6 ]
Moore, Penny L. [1 ,2 ,7 ,14 ]
机构：
[1] Natl Inst Communicable Dis, Natl Hlth Lab Serv, Johannesburg, South Africa
[2] Univ Witwatersrand, Sch Pathol, South African Med Res Council Antibody Immun Res, Johannesburg, South Africa
[3] Univ Pretoria, Fac Hlth Sci, Dept Immunol, Pretoria, South Africa
[4] Tshwane Dist Hosp, Pretoria, South Africa
[5] Steve Biko Acad Hosp, Dept Internal Med, Div Infect Dis, Pretoria, South Africa
[6] Univ Pretoria, Pretoria, South Africa
[7] Univ Cape Town, Inst Infect Dis & Mol Med, Cape Town, South Africa
[8] Univ Cape Town, Dept Pathol, Div Med Virol, Cape Town, South Africa
[9] Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Cape Town, South Africa
[10] Univ Cape Town, Dept Med, Cape Town, South Africa
[11] Groote Schuur Hosp, Cape Town, South Africa
[12] Univ Cape Town, Hatter Inst Cardiovasc Res Africa, Fac Hlth Sci, Cape Town, South Africa
[13] Univ Cape Town, Hatter Inst Cardiovasc Res Africa, Fac Hlth Sci, Cape Town, South Africa
[14] Ctr AIDS Programme Res South Africa, Durban, South Africa
来源：
CELL REPORTS MEDICINE | 2023年 / 4卷 / 01期
基金：
新加坡国家研究基金会; 英国医学研究理事会;
关键词：
FC EFFECTOR FUNCTIONS; NEUTRALIZING ANTIBODIES; DELTA; BETA;
D O I：
10.1016/j.xcrm.2022.100910
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 FcgRIIIa 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.
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页数：14
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