Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells.
Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells.
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DOI：
10.1038/s41541-021-00376-7
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发表时间：
2021-09-06
期刊：
影响因子：
9.2
通讯作者：
Crotty S
中科院分区：
文献类型：
--
作者：
Lee JH;Toy L;Kos JT;Safonova Y;Schief WR;Havenar-Daughton C;Watson CT;Crotty S
成功的HIV疫苗引发广泛中和抗体（bnAb）必须克服能够激活幼稚前体B细胞的障碍，所述幼稚前体B细胞编码其种系B细胞受体（BCR）内的允许广泛中和表位识别的特征。了解bnAb前体B细胞是否以足够的频率在受HIV严重影响的社区中的个体中循环可能是重要的。使用生殖系靶向eOD-GT 8免疫原和基于液滴的高通量单细胞BCR测序，我们证明了可以有效地筛选来自多个供体的大量配对BCR序列，以阐明罕见的幼稚VRC 01类B细胞的前体频率。此外，我们分析了IGHV 1 -2等位基因在三个不同队列中的使用情况;我们发现，传统上被认为与VRC 01类应答不相容的IGHV 1 -2等位基因在各种人群中相对常见，IGHV 1 -2内的种系变异与幼稚BCR库中的基因使用频率相关。
A successful HIV vaccine eliciting broadly neutralizing antibodies (bnAbs) must overcome the hurdle of being able to activate naive precursor B cells encoding features within their germline B cell receptors (BCR) that allow recognition of broadly neutralizing epitopes. Knowledge of whether bnAb precursor B cells are circulating at sufficient frequencies within individuals in communities heavily impacted by HIV may be important. Using a germline-targeting eOD-GT8 immunogen and high-throughput droplet-based single-cell BCR sequencing, we demonstrate that large numbers of paired BCR sequences from multiple donors can be efficiently screened to elucidate precursor frequencies of rare, naive VRC01-class B cells. Further, we analyzed IGHV1-2 allelic usage among three different cohorts; we find that IGHV1-2 alleles traditionally thought to be incompatible with VRC01-class responses are relatively common in various human populations and that germline variation within IGHV1-2 associates with gene usage frequencies in the naive BCR repertoire.
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影响因子：
15.3
作者：
Dosenovic, Pia;Pettersson, Anna-Klara;McGuire, Andrew T.
通讯作者：
McGuire, Andrew T.
影响因子：
--
作者：
Giudicelli, Veronique;Brochet, Xavier;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
影响因子：
5.9
作者：
Goldstein, Leonard D.;Chen, Ying-Jiun J.;Seshagiri, Somasekar
通讯作者：
Seshagiri, Somasekar
DOI：
10.1126/science.1234150
发表时间：
2013-05-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jardine J;Julien JP;Menis S;Ota T;Kalyuzhniy O;McGuire A;Sok D;Huang PS;MacPherson S;Jones M;Nieusma T;Mathison J;Baker D;Ward AB;Burton DR;Stamatatos L;Nemazee D;Wilson IA;Schief WR
通讯作者：
Schief WR
有效V1V2定向HIV中和抗体的发育途径。
影响因子：
64.8
作者：
Doria-Rose, Nicole A.;Schramm, Chaim A.;Gorman, Jason;Moore, Penny L.;Bhiman, Jinal N.;DeKosky, Brandon J.;Ernandes, Michael J.;Georgiev, Ivelin S.;Kim, Helen J.;Pancera, Marie;Staupe, Ryan P.;Altae-Tran, Han R.;Bailer, Robert T.;Crooks, Ema T.;Cupo, Albert;Druz, Aliaksandr;Garrett, Nigel J.;Hoi, Kam H.;Kong, Rui;Louder, Mark K.;Longo, Nancy S.;McKee, Krisha;Nonyane, Molati;O'Dell, Sijy;Roark, Ryan S.;Rudicell, Rebecca S.;Schmidt, Stephen D.;Sheward, Daniel J.;Soto, Cinque;Wibmer, Constantinos Kurt;Yang, Yongping;Zhang, Zhenhai;Mullikin, James C.;Binley, James M.;Sanders, Rogier W.;Wilson, Ian A.;Moore, John P.;Ward, Andrew B.;Georgiou, George;Williamson, Carolyn;Karim, Salim S. Abdool;Morris, Lynn;Kwong, Peter D.;Shapiro, Lawrence;Mascola, John R.
通讯作者：
Mascola, John R.