Medical Research Council, University of Glasgow Centre for Virus Research, Henry Wellcome Building for Comparative Medical Sciences, 464 Bearsden Road, Glasgow G61 1QH, UK.
Viruses. 2011 Oct;3(10):1870-90. doi: 10.3390/v3101870. Epub 2011 Oct 13.
One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env), a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3) of Env. For feline immunodeficiency virus (FIV), as well as the related human immunodeficiency virus-1 (HIV-1), little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1.
在设计有效的慢病毒疫苗时,必须克服的主要障碍之一是慢病毒能够进化以逃避中和抗体。中和抗体的主要靶标是高度可变的病毒包膜糖蛋白(Env),该糖蛋白对于病毒进入至关重要,包含可变区和保守区。由于 Env 的复杂三聚体性质,受体结合所需的保守表位存在空间位阻,因此抗体无法接触到这些表位。相反,体液反应针对可变结构域上的诱饵免疫优势表位,例如 Env 的第三个高变环(V3)。对于猫免疫缺陷病毒(FIV)以及相关的人类免疫缺陷病毒-1(HIV-1),人们对导致广泛中和抗体产生的因素知之甚少。在感染 FIV 的猫和感染 HIV-1 的患者中,很少发现含有能够中和其他分支分离株的抗体的血浆样本。在这篇综述中,我们检查了对 FIV 的中和反应,并将其与对 HIV 的反应进行了比较和对比。我们询问 FIV 感染是否会诱导广泛中和抗体,并讨论了在 FIV 感染中研究中和抗体的相对价值,以开发针对包括 HIV-1 在内的慢病毒感染的更有效疫苗策略。