Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines.
Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines.
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DOI：
10.1126/scitranslmed.abn9243
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发表时间：
2022-04-27
影响因子：
17.1
通讯作者：
Alter G
中科院分区：
文献类型：
--
作者：
Bartsch YC;Tong X;Kang J;Avendaño MJ;Serrano EF;García-Salum T;Pardo-Roa C;Riquelme A;Cai Y;Renzi I;Stewart-Jones G;Chen B;Medina RA;Alter G
SARS-CoV-2 的 Omicron 变体已被证明可以逃避疫苗接种或先前感染引起的中和抗体。尽管 Omicron 变种在全球范围内急剧传播，即使在高度接种疫苗的人群中，死亡率也没有随之增加。这些数据表明，抗体介导的病毒中和之外的免疫机制可以预防严重疾病。除了中和病原体之外，抗体还有助于通过 Fc 效应器机制控制和清除感染。在这里，我们使用来自接受三种 SARS-CoV-2 疫苗之一的个体的样本，探讨了疫苗诱导的抗体驱动针对 Omicron 变体的 Fc 效应器活性的能力。尽管在接受 BNT162b2、mRNA-1273 和 CoronaVac 疫苗的个体样本中，与 Omicron 变体受体结合域 (RBD) 结合的 IgM、IgA 和 IgG 大量丧失，但针对全长 Omicron Spike 蛋白的稳定结合仍然保持。在接受 CoronaVac 疫苗的个体样本中，RBD 结合 IgG 受损伴随着交叉 RBD 特异性抗体 Fcγ 受体 (FcγR) 结合的丧失，但在 mRNA 疫苗的接受者中保留了 RBD 特异性 FcγR2a 和 FcγR3a 结合。相反，在所有三种疫苗中，Spike 蛋白特异性抗体都表现出与 FcγR 的持久但减少的结合，尽管在来自 mRNA 疫苗接受者的样本中观察到更高的结合。这与 FcγR2a 和 FcγR3a 结合抗体的保存以及刺突蛋白特异性抗体依赖性自然杀伤细胞激活抗体的维持有关。因此，尽管失去了 Omicron 中和作用，但疫苗诱导的 Spike 蛋白特异性抗体继续驱动 Fc 效应器功能，这表明额外中和抗体有能力有助于疾病控制。由 mRNA 或灭活病毒疫苗诱导的 SARS-CoV-2 特异性抗体维持 Omicron 变体特异性 Fc 介导的效应机制。
The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or prior infection. Despite the dramatic global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc-effector mechanisms. Here we probed the ability of vaccine-induced antibodies to drive Fc-effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant Receptor Binding Domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of cross RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, though higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activating antibodies. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc-effector functions, suggesting a capacity for extra-neutralizing antibodies to contribute to disease control. SARS-CoV-2-specific antibodies induced by mRNA or inactivated virus vaccines maintain Omicron variant-specific Fc-mediated effector mechanisms.
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DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
影响因子：
3.7
作者：
Chan CEZ;Seah SGK;Chye H;Massey S;Torres M;Lim APC;Wong SKK;Neo JJY;Wong PS;Lim JH;Loh GSL;Wang D;Boyd-Kirkup JD;Guan S;Thakkar D;Teo GH;Purushotorman K;Hutchinson PE;Young BE;Low JG;MacAry PA;Hentze H;Prativadibhayankara VS;Ethirajulu K;Comer JE;Tseng CK;Barrett ADT;Ingram PJ;Brasel T;Hanson BJ
通讯作者：
Hanson BJ
影响因子：
56.9
作者：
Cai, Yongfei;Zhang, Jun;Chen, Bing
通讯作者：
Chen, Bing
影响因子：
11.8
作者：
Plotkin, Stanley A.
通讯作者：
Plotkin, Stanley A.
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group