Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor.
Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor.
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DOI：
10.1126/scitranslmed.3008992
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发表时间：
2014-07-02
影响因子：
17.1
通讯作者：
Nabel GJ
中科院分区：
文献类型：
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作者：
Pegu A;Yang ZY;Boyington JC;Wu L;Ko SY;Schmidt SD;McKee K;Kong WP;Shi W;Chen X;Todd JP;Letvin NL;Huang J;Nason MC;Hoxie JA;Kwong PD;Connors M;Rao SS;Mascola JR;Nabel GJ
HIV-1感染依赖于其包膜（Env）糖蛋白与特定细胞表面受体相互作用介导的有效病毒进入。被动或主动免疫产生的保护性抗病毒抗体必须防止这些相互作用。由于HIV-1 Env高度可变，人们的注意力也集中在阻断HIV-1原代细胞受体CD4上。因此，我们分析了三种有效的中和单克隆抗体（mab）对HIV-1 Env的体内保护效果，并与针对CD4受体的抗体进行了比较。研究了猴/HIV （SHIV）感染恒河猴粘膜后的保护作用。尽管抗CD4抗体在体外具有相当或更高的中和效力，但在体内并不能提供有效的保护，而hiv -1特异性单克隆抗体VRC01、10E8和PG9分别靶向CD4结合位点、膜近端和V1V2聚糖Env区域，尽管相对效力不同，但却能提供完全的保护。这些发现证明了针对HIV-1 Env的广泛中和抗体的保护作用，并表明靶向HIV-1 Env比靶向细胞表面受体CD4更能预防HIV-1传播。
HIV-1 infection depends on effective viral entry mediated by the interaction of its envelope (Env) glycoprotein with specific cell surface receptors. Protective antiviral antibodies generated by passive or active immunization must prevent these interactions. Because the HIV-1 Env is highly variable, attention has also focused on blocking the HIV-1 primary cell receptor CD4. We therefore analyzed the in vivo protective efficacy of three potent neutralizing monoclonal antibodies (mAbs) to HIV-1 Env compared to an antibody against the CD4 receptor. Protection was assessed after mucosal challenge of rhesus macaques with simian/HIV (SHIV). Despite its comparable or greater neutralization potency in vitro, the anti-CD4 antibody did not provide effective protection in vivo, whereas the HIV-1–specific mAbs VRC01, 10E8, and PG9, targeting the CD4 binding site, membrane-proximal, and V1V2 glycan Env regions, respectively, conferred complete protection, albeit at different relative potencies. These findings demonstrate the protective efficacy of broadly neutralizing antibodies directed to the HIV-1 Env and suggest that targeting the HIV-1 Env is preferable to the cell surface receptor CD4 for the prevention of HIV-1 transmission.