A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike.
A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike.
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公共抗体类识别暴露在SARS-CoV-2刺突开放构象上的S2表位。
DOI：
10.1038/s41467-022-32232-0
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发表时间：
2022-08-04
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
描述SARS-CoV-2感染和疫苗接种引起的抗体的来源和性质对于理解其益处和潜在缺点至关重要。因此，我们通过流式细胞术和单细胞测序研究了未暴露个体中SARS-CoV-2刺突（S）反应性B细胞库。我们发现约82%的SARS-CoV-2 S反应性B细胞具有幼稚表型，这代表了总人类幼稚B细胞的异常高的比例（约0.1%）。大约10%的这些幼稚S反应性B细胞共享IGHV 1 -69/IGKV 3 -11 B细胞受体配对，与完整幼稚库相比富集18倍。在SARS-CoV-2感染后，我们报道了与非特异性记忆库相比，S-反应性记忆B细胞中IGHV 1 -69/IGKV 3 -11 B细胞受体配对的平均37倍富集。这类B细胞靶向S2亚基上先前未定义的非中和表位，当它们由于不稳定性而从天然融合前状态转变时，该表位暴露在批准的疫苗中使用的S蛋白上。这些发现有助于指导SARS-CoV-2疫苗的改进。为了充分了解SARS-CoV-2疫苗接种的潜在缺点，有必要描述在免疫过程中以及感染过程中引发的抗体的特性。通过对SARS-CoV-2刺突反应性B细胞库的研究，作者鉴定了感染后富集的B细胞亚群，并且几乎完全靶向以异常形式存在的非中和S2表位。
Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-CoV-2 S-reactive B cells harbor a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.1%). Approximately 10% of these naive S-reactive B cells share an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines. To fully understand the potential shortcomings of SARS-CoV-2 vaccination, it is necessary to delineate the properties of the antibodies elicited, during immunization, and also infection. Through investigation of the SARS-CoV-2 spike-reactive B cell repertoire, authors identify following infection, a subset of B cells enriched and almost exclusively target a non-neutralizing S2 epitope present in aberrant forms.
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影响因子：
32.4
作者：
Dugan HL;Stamper CT;Li L;Changrob S;Asby NW;Halfmann PJ;Zheng NY;Huang M;Shaw DG;Cobb MS;Erickson SA;Guthmiller JJ;Stovicek O;Wang J;Winkler ES;Madariaga ML;Shanmugarajah K;Jansen MO;Amanat F;Stewart I;Utset HA;Huang J;Nelson CA;Dai YN;Hall PD;Jedrzejczak RP;Joachimiak A;Krammer F;Diamond MS;Fremont DH;Kawaoka Y;Wilson PC
通讯作者：
Wilson PC
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
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
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
影响因子：
8.8
作者：
Chen EC;Gilchuk P;Zost SJ;Suryadevara N;Winkler ES;Cabel CR;Binshtein E;Chen RE;Sutton RE;Rodriguez J;Day S;Myers L;Trivette A;Williams JK;Davidson E;Li S;Doranz BJ;Campos SK;Carnahan RH;Thorne CA;Diamond MS;Crowe JE Jr
通讯作者：
Crowe JE Jr