Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.
Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.
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DOI：
10.1371/journal.pone.0008805
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发表时间：
2010-01-20
期刊：
影响因子：
3.7
通讯作者：
Lanzavecchia A
中科院分区：
文献类型：
--
作者：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
分离能够中和多种原发性人类免疫缺陷病毒1型（HIV - 1）分离株的人单克隆抗体（mAbs）以及对HIV - 1感染后人中和抗体B细胞反应进行表征是重要目标，这些目标对于设计一种有效的基于抗体的疫苗至关重要。
我们使感染了不同HIV - 1分支的个体的IgG⁺记忆B细胞永生化，并根据跨分支且相对有效的血浆中和谱进行选择。在多个平行试验中，使用各种重组形式的包膜糖蛋白（Env）对培养上清液进行筛选。我们分离出58种单克隆抗体，它们定位于不同的Env表面，其中大多数显示出中和活性。特别是一种针对gp120上靠近CD4结合位点的新表位的单克隆抗体（HJ16），它选择性地中和了一组多分支的二级HIV - 1假病毒，并且其反应性在广度上与另一种针对CD4结合位点的中和性单克隆抗体b12相当，但在中和特异性上有所不同。第二种单克隆抗体（HGN194）结合V3冠中的一个保守表位，中和了所有一级以及一部分所测试的二级假病毒，无论其分支如何。第三种单克隆抗体（HK20）具有广泛的中和活性，特别是作为Fab片段时，它识别gp41的HR - 1区域中一个高度保守的表位，但在其活性上表现出显著的依赖于检测方法的选择性。
这项研究表明，通过使用适当的筛选方法，可以分离出很大比例的产生具有HIV - 1中和活性的单克隆抗体的记忆B细胞。其中三种单克隆抗体显示出不寻常的中和广度，因此加入到当前具有被动保护潜力和基于模板的疫苗设计潜力的HIV - 1中和抗体组合中。
The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. We immortalized IgG+ memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.
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影响因子：
56.9
作者：
Haynes, BF;Fleming, J;Alam, SM
通讯作者：
Alam, SM
DOI：
10.1016/j.bbrc.2006.07.163
发表时间：
2006-09-29
影响因子：
3.1
作者：
Choudhry, Vidita;Zhang, Mei-Yun;Dimitrov, Dimiter S.
通讯作者：
Dimitrov, Dimiter S.
影响因子：
5.4
作者：
Gorny, MK;Revesz, K;Zolla-Pazner, S
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Zolla-Pazner, S
影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF
国际艾滋病毒中和试验比较网络：NeutNet 报告。
影响因子：
3.7
作者：
Fenyo, Eva Maria;Heath, Alan;Dispinseri, Stefania;Holmes, Harvey;Lusso, Paolo;Zolla-Pazner, Susan;Donners, Helen;Heyndrickx, Leo;Alcami, Jose;Bongertz, Vera;Jassoy, Christian;Malnati, Mauro;Montefiori, David;Moog, Christiane;Morris, Lynn;Osmanov, Saladin;Polonis, Victoria;Sattentau, Quentin;Schuitemaker, Hanneke;Sutthent, Ruengpung;Wrin, Terri;Scarlatti, Gabriella
通讯作者：
Scarlatti, Gabriella