National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg 2131, South Africa.
SA MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg 2001, South Africa.
Cell Rep Med. 2022 Jan 17;3(2):100510. doi: 10.1016/j.xcrm.2022.100510. eCollection 2022 Feb 15.
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.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起关注的变异株（VOCs）表现出对中和抗体的逃逸，这引起了人们对疫苗有效性的担忧。然而，虽然抗体的非中和细胞毒性功能与改善疾病结局和疫苗保护相关，但 VOC 对 Fc 效应功能的逃逸仍未得到明确界定。此外，VOC 是否像中和作用那样触发具有改变特异性的 Fc 功能尚不清楚。在这里，我们证明 Beta VOC 会部分逃避原始（D614G）变体感染个体中的 Fc 效应子活性。然而，并非所有功能都受到同等影响，这表明介导不同 Fc 功能的抗体具有不同的靶向性。此外，与 D614G 感染或 Ad26.COV2.S 疫苗接种个体相比，Beta 和 Delta 感染会引发对全球 VOC 具有显著改善的 Fc 交叉反应性的反应。这表明，与中和作用一样，感染的刺突序列会影响 Fc 效应子功能。这些数据对包含 VOC 的疫苗策略具有重要意义，表明这些策略可能会诱导更广泛的 Fc 效应子反应。
