Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse.
Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse.
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DOI：
10.1016/j.virol.2006.09.029
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发表时间：
2007-04-25
期刊：
影响因子：
3.7
通讯作者：
Prabhakar BS
中科院分区：
文献类型：
--
作者：
Coughlin M;Lou G;Martinez O;Masterman SK;Olsen OA;Moksa AA;Farzan M;Babcook JS;Prabhakar BS
用中和性人单克隆抗体（mAb）进行被动治疗可能是对抗严重急性呼吸综合征冠状病毒（SARS-CoV）的有效治疗方法。利用人免疫球蛋白转基因小鼠XenoMouse®，我们产生了完全人SARS-CoV刺突（S）蛋白特异性抗体。检测抗体对重组S1蛋白的反应性，200种抗体与重组S1蛋白反应。27个抗体中和200 TCID 50 SARS-CoV（Urbani）。此外，还发现了57种可能对S2具有特异性的中和抗体。用几种S1重组蛋白实现了结合区的定位。大多数S1反应性中和mAb与RBD结合，aa 318-510。然而，两种S1特异性mAb与RBD上游aa 12和261之间的结构域反应。免疫球蛋白基因序列分析表明至少有8种不同的结合特异性。独特的人单克隆抗体可用作鸡尾酒，其将同时靶向几个中和表位并防止逃逸突变体的出现。
Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse®, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID50 SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318–510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.
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影响因子：
4.6
作者：
Lin YS;Lin CF;Fang YT;Kuo YM;Liao PC;Yeh TM;Hwa KY;Shieh CC;Yen JH;Wang HJ;Su IJ;Lei HY
通讯作者：
Lei HY
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
5.4
作者：
Sui, JH;Li, WH;Marasco, WA
通讯作者：
Marasco, WA
DOI：
10.1007/s10096-004-1271-9
发表时间：
2005-01
期刊：
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
影响因子：
--
作者：
Cheng Y;Wong R;Soo YO;Wong WS;Lee CK;Ng MH;Chan P;Wong KC;Leung CB;Cheng G
通讯作者：
Cheng G
DOI：
10.1016/j.bbrc.2005.07.002
发表时间：
2005-09-09
影响因子：
3.1
作者：
Rathanaswami, P;Roalstad, S;Babcook, J
通讯作者：
Babcook, J