ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.
ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.
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DOI：
10.1038/s41590-023-01513-1
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发表时间：
2023-07
影响因子：
30.5
通讯作者：
Alter, Galit
中科院分区：
文献类型：
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作者：
Kaplonek, Paulina;Cizmeci, Deniz;Kwatra, Gaurav;Izu, Alane;Lee, Jessica Shih-Lu;Bertera, Harry L.;Fischinger, Stephanie;Mann, Colin;Amanat, Fatima;Wang, Wenjun;Koen, Anthonet L.;Fairlie, Lee;Cutland, Clare L.;Ahmed, Khatija;Dheda, Keertan;Barnabas, Shaun L.;Bhorat, Qasim Ebrahim;Briner, Carmen;Krammer, Florian;Saphire, Erica Ollman;Gilbert, Sarah C.;Lambe, Teresa;Pollard, Andrew J.;Nunes, Marta;Wuhrer, Manfred;Lauffenburger, Douglas A.;Madhi, Shabir A.;Alter, Galit
尽管COVID-19疫苗取得了成功，但令人担忧的严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）变体已经出现，可能导致突破性感染。尽管对严重疾病的保护在很大程度上得到了保存，但人类保护的免疫介质仍然不明确。我们对参加南非临床试验的ChAdOx1 nCoV-19 （AZD1222）疫苗接种者进行了一项亚研究。在感染前的免疫原性峰值，免疫球蛋白（Ig） g1结合抗体滴度无差异；然而，疫苗在各组间诱导了不同的fc受体结合抗体。抵抗COVID-19的疫苗接种者只携带fc γ r3b结合抗体。相比之下，在经历突破的个体中，观察到与丰富的FcγR2B结合相关的IgA和IgG3增强。不能结合FcγR3B的抗体导致免疫复合物清除并导致炎症级联反应。与FcγR3B结合的差异抗体与sars - cov -2特异性抗体的fc糖基化差异有关。这些数据可能表明，特定的fc γ r3b介导的抗体功能谱是对COVID-19免疫的关键标记。Kaplonek等人对接种ChAdOx1 ncov -19疫苗的个体进行了前瞻性研究，这些个体继续经历突破性的COVID感染。他们报告了一种抗体Fc谱，其特征是更容易发生突破性感染的个体的FcgR2b较高，Fcgr3b较低。
Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed in immunoglobulin (Ig)G1-binding antibody titers; however, the vaccine induced different Fc-receptor-binding antibodies across groups. Vaccinees who resisted COVID-19 exclusively mounted FcγR3B-binding antibodies. In contrast, enhanced IgA and IgG3, linked to enriched FcγR2B binding, was observed in individuals who experienced breakthrough. Antibodies unable to bind to FcγR3B led to immune complex clearance and resulted in inflammatory cascades. Differential antibody binding to FcγR3B was linked to Fc-glycosylation differences in SARS-CoV-2-specific antibodies. These data potentially point to specific FcγR3B-mediated antibody functional profiles as critical markers of immunity against COVID-19. Kaplonek et al. provide a prospective look at ChAdOx1 nCoV-19-vaccinated individuals who go on to experience breakthrough COVID infections. They report an antibody Fc profile characterized by higher FcgR2b and reduced Fcgr3b for individuals who are more susceptible to breakthrough infections.
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DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
趋化因子在调节慢性病毒感染过程中调节CD8 T细胞反应的作用。
影响因子：
6.7
作者：
Crawford A;Angelosanto JM;Nadwodny KL;Blackburn SD;Wherry EJ
通讯作者：
Wherry EJ
影响因子：
29.7
作者：
Bournazos S;Wang TT;Dahan R;Maamary J;Ravetch JV
通讯作者：
Ravetch JV
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
7.8
作者：
Alter G;Ottenhoff THM;Joosten SA
通讯作者：
Joosten SA