严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）疫苗引发不同的Fc效应器功能。
SARS-CoV-2 vaccines elicit differential Fc effector functions.
作者信息
Manamela Nelia P, Motsoeneng Boitumelo M, Spencer Holly, Hermanus Tandile, Mzindle Nonkululeko, Ayres Frances, Makhado Zanele, Serage Rudolph, Gray Glenda G, Bekker Linda-Gail, Madhi Shabir A, Moore Penny L, Richardson Simone I
机构信息
South African Medical Research Council Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
出版信息
iScience. 2025 Jul 9;28(8):113084. doi: 10.1016/j.isci.2025.113084. eCollection 2025 Aug 15.
In addition to neutralization, Fc effector function contributes to vaccine-mediated protection against severe SARS-CoV-2 infection. However, differential coordination and cross-reactivity of Fc effector functions across vaccines is not clearly defined. A secondary analysis of three vaccines with BNT162b2, Ad26.CoV2.S (NCT04838795), and ChAdOx1 nCoV-19 (NCT04444674) reveals that BNT162b2 elicits the highest levels of binding, neutralization, and Fc effector function with antibody-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), and complement deposition (ADCD) significantly differing by vaccine modality. Ad26.CoV2.S showed low ADCD activity before a homologous boost, which significantly increased this function. BNT162b2 vaccination triggered higher levels of cross-reactive neutralization, ADCC and ADCP than the adenoviral vaccines, while ChAdOx1 nCoV-19 exhibited higher ADCD cross-reactivity. Coordination between functions all varied by modality, with vaccination eliciting neutralization and binding correlations with ADCC for BNT162b2, but with ADCD following Ad26.CoV2.S vaccination. This supports the optimization of Fc effector functions for improved polyfunctional vaccine design.
除了中和作用外，Fc效应功能有助于疫苗介导的针对严重SARS-CoV-2感染的保护作用。然而，不同疫苗之间Fc效应功能的差异协同作用和交叉反应性尚未明确界定。对三种疫苗BNT162b2、Ad26.CoV2.S（NCT04838795）和ChAdOx1 nCoV-19（NCT04444674）的二次分析表明，BNT162b2引发的结合、中和及Fc效应功能水平最高，其抗体依赖性细胞毒性（ADCC）、吞噬作用（ADCP）和补体沉积（ADCD）因疫苗类型的不同而有显著差异。Ad26.CoV2.S在同源加强免疫前显示出较低的ADCD活性，加强免疫后该功能显著增强。与腺病毒疫苗相比，BNT162b2疫苗接种引发的交叉反应性中和、ADCC和ADCP水平更高，而ChAdOx1 nCoV-19表现出更高的ADCD交叉反应性。不同功能之间的协同作用因疫苗类型而异，BNT162b2疫苗接种引发的中和与结合与ADCC相关，而Ad26.CoV2.S疫苗接种后则与ADCD相关。这支持了优化Fc效应功能以改进多功能疫苗设计。
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