Focusing the immune response on the V3 loop, a neutralizing epitope of the HIV-1 gp120 envelope.
Focusing the immune response on the V3 loop, a neutralizing epitope of the HIV-1 gp120 envelope.
复制标题
将免疫反应集中在 V3 环上，V3 环是 HIV-1 gp120 包膜的中和表位。
DOI：
10.1016/j.virol.2007.09.024
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Lu,Shan
中科院分区：
文献类型：
--
作者：
Zolla-Pazner,Susan;Cohen,SandraSharpe;Krachmarov,Chavdar;Wang,Shixia;Pinter,Abraham;Lu,Shan
用一种新的方案免疫家兔，该方案旨在将免疫应答集中在HIV-1 gp 120的单个中和表位上，从而优先诱导中和抗体（Abs）。用来自携带GPGR V3基序的进化枝A Env和/或携带GPGQ V3基序的进化枝C Env的gp 120 DNA引发动物，并用含有来自进化枝A、B和/或C的V3序列的一种或多种融合蛋白加强。免疫血清中和了4个1级原代分离株中的3个，包括与免疫菌株异源的菌株，并且证明了对1级Env中携带来自进化枝A1、AG、B、AE或F的共有V3序列的V3嵌合假病毒的有效交叉进化枝中和活性。用进化枝C gp 120 DNA和来自进化枝A、B和C的V3融合蛋白的组合引起最广泛和最有效的中和反应。中和活性主要归因于V3特异性Ab。结果表明，免疫应答可以集中在中和表位上，并显示诱导的抗V3 Ab识别不同的V3环组。
Rabbits were immunized with a novel regimen designed to focus the immune response on a single neutralizing epitope of HIV-1 gp120 and thereby preferentially induce neutralizing antibodies (Abs). Animals were primed with gp120 DNA from a clade A Env bearing the GPGR V3 motif and/or a clade C Env bearing the GPGQ V3 motif, and boosted with one or more fusion proteins containing V3 sequences from clades A, B and/or C. Immune sera neutralized three of four Tier 1 primary isolates, including strains heterologous to the immunizing strains, and potent cross-clade-neutralizing activity was demonstrated against V3 chimeric pseudoviruses carrying in a Tier 1 Env, the consensus V3 sequences from clades A1, AG, B, AE, or F. The broadest and most potent neutralizing responses were elicited with the clade C gp120 DNA and a combination of V3-fusion proteins from clades A, B and C. Neutralizing activity was primarily due to V3-specific Abs. The results demonstrate that the immune response can be focused on a neutralizing epitope and show that the anti-V3 Abs induced recognize a diverse set of V3 loops.