Eliciting neutralizing antibodies with gp120 outer domain constructs based on M-group consensus sequence.
Eliciting neutralizing antibodies with gp120 outer domain constructs based on M-group consensus sequence.
复制标题
使用基于 M 组共有序列的 gp120 外域构建体引发中和抗体。
DOI：
10.1016/j.virol.2014.06.006
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cho,MichaelW
中科院分区：
文献类型：
--
作者：
Qin,Yali;Banasik,Marisa;Kim,SoonJeung;Penn-Nicholson,Adam;Habte,HabtomH;LaBranche,Celia;Montefiori,DavidC;Wang,Chong;Cho,MichaelW
One strategy being evaluated for HIV-1 vaccine development is focusing immune responses towards neutralizing epitopes on the gp120 outer domain (OD) by removing the immunodominant, but non-neutralizing, inner domain. Previous OD constructs have not elicited strong neutralizing antibodies (nAbs). We constructed two immunogens, a monomeric gp120-OD and a trimeric gp120-OD×3, based on an M group consensus sequence (MCON6). Their biochemical and immunological properties were compared with intact gp120. Results indicated better preservation of critical neutralizing epitopes on gp120-OD×3. In contrast to previous studies, our immunogens induced potent, cross-reactive nAbs in rabbits. Although nAbs primarily targeted Tier 1 viruses, they exhibited significant breadth. Epitope mapping analyses indicated that nAbs primarily targeted conserved V3 loop elements. Although the potency and breadth of nAbs were similar for all three immunogens, nAb induction kinetics indicated that gp120-OD×3 was superior to gp120-OD, suggesting that gp120-OD×3 is a promising prototype for further gp120 OD-based immunogen development.
