Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?
Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?
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DOI：
10.1038/nm.1949
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发表时间：
2009-08-01
期刊：
影响因子：
82.9
通讯作者：
Mascola, John R.
中科院分区：
文献类型：
--
作者：
Stamatatos, Leonidas;Morris, Lynn;Mascola, John R.
大多数现有的病毒疫苗产生的抗体要么阻止初始感染，要么在病毒引起疾病之前帮助根除病毒。对于HIV-1，引发保护性中和抗体（NAb）的障碍往往似乎是不可逾越的。HIV特异性NAb的靶点是病毒包膜糖蛋白（Env），其氨基酸序列和糖基化模式高度可变。HIV-1 Env的保守元件似乎免疫原性差，并且先前通过疫苗接种产生广泛反应性NAb的尝试已被证明无效。然而，最近的研究表明，在一些HIV-1感染者的血清中，可以中和多种HIV-1分离株。对这些血清的详细分析为广泛反应性NAb靶向的病毒表位提供了新的见解。这里讨论的研究结果表明，对HIV-1的天然NAb反应可以为未来的疫苗设计提供信息。基于结构的疫苗设计的协同努力将有助于指导改进的基于抗体的HIV-1疫苗的开发。
Most existing viral vaccines generate antibodies that either block initial infection or help eradicate the virus before it can cause disease. For HIV-1, obstacles to eliciting protective neutralizing antibodies (NAbs) have often seemed insurmountable. The target of HIV-specific NAbs, the viral envelope glycoprotein (Env), is highly variable in amino acid sequence and glycosylation pattern. Conserved elements of HIV-1 Env seem to be poorly immunogenic, and previous attempts to generate broadly reactive NAbs by vaccination have proven ineffective. However, recent studies show that in the sera of some HIV-1-infected individuals can neutralize diverse HIV-1 isolates. Detailed analyses of these sera provide new insights into the viral epitopes targeted by broadly reactive NAbs. The findings discussed here suggest that the natural NAb response to HIV-1 can inform future vaccine design. A concerted effort of structure-based vaccine design will help guide the development of improved antibody-based vaccines for HIV-1.