Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.
Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.
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DOI：
10.1126/scitranslmed.aai7514
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发表时间：
2017-03-15
影响因子：
17.1
通讯作者：
Haynes BF
中科院分区：
文献类型：
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作者：
Bonsignori M;Kreider EF;Fera D;Meyerhoff RR;Bradley T;Wiehe K;Alam SM;Aussedat B;Walkowicz WE;Hwang KK;Saunders KO;Zhang R;Gladden MA;Monroe A;Kumar A;Xia SM;Cooper M;Louder MK;McKee K;Bailer RT;Pier BW;Jette CA;Kelsoe G;Williams WB;Morris L;Kappes J;Wagh K;Kamanga G;Cohen MS;Hraber PT;Montefiori DC;Trama A;Liao HX;Kepler TB;Moody MA;Gao F;Danishefsky SJ;Mascola JR;Shaw GM;Hahn BH;Harrison SC;Korber BT;Haynes BF
预防性HIV-1疫苗应诱导HIV-1特异性广泛中和抗体（bnAbs）。然而，bnAbs通常需要高水平的体细胞超突变（SHM）才能获得宽度，目前的疫苗策略尚未成功诱导bnAbs。由于针对HIV-1包膜蛋白第三可变环（V3）附近的糖基化位点的bnAbs需要有限的SHM，因此V3-聚糖表位是一个有吸引力的疫苗靶标。通过研究多种V3-glycan B细胞系之间的合作以及它们在5年感染过程中与自身病毒的共同进化，我们确定了一个V3-glycan bnAb个体发生的关键事件。选择了两种用于病毒逃逸突变的自体中和抗体谱系，从而允许V3-glycan bnAb谱系的起始和亲和成熟。启动bnAb谱系所需的核苷酸替换发生在激活诱导胞苷脱氨酶活性的低概率位点。B细胞系的合作和对bnAb活性至关重要的不可能的突变定义了导致这个v3 -聚糖bnAb谱系广度的必要事件。这些发现可能在一定程度上解释了为什么很少启动V3-glycan bnAbs，并提出了一种诱导类似V3-glycan bnAbs的免疫策略。
A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.
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影响因子：
5.4
作者：
Go, Eden P.;Herschhorn, Alon;Desaire, Heather
通讯作者：
Desaire, Heather
影响因子：
16.8
作者：
Kong, Leopold;Lee, Jeong Hyun;Doores, Katie J.;Murin, Charles D.;Julien, Jean-Philippe;McBride, Ryan;Liu, Yan;Marozsan, Andre;Cupo, Albert;Klasse, Per-Johan;Hoffenberg, Simon;Caulfield, Michael;King, C. Richter;Hua, Yuanzi;Le, Khoa M.;Khayat, Reza;Deller, Marc C.;Clayton, Thomas;Tien, Henry;Feizi, Ten;Sanders, Rogier W.;Paulson, James C.;Moore, John P.;Stanfield, Robyn L.;Burton, Dennis R.;Ward, Andrew B.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
影响因子：
--
作者：
Kepler TB
通讯作者：
Kepler TB
影响因子：
4.3
作者：
Gnanakaran S;Daniels MG;Bhattacharya T;Lapedes AS;Sethi A;Li M;Tang H;Greene K;Gao H;Haynes BF;Cohen MS;Shaw GM;Seaman MS;Kumar A;Gao F;Montefiori DC;Korber B
通讯作者：
Korber B
影响因子：
46.9
作者：
通讯作者：
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