Antibody-Dependent Cell-Mediated Viral Inhibition Emerges after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys Coincident with gp140-Binding Antibodies and Is Effective against Neutralization-Resistant Viruses
Antibody-Dependent Cell-Mediated Viral Inhibition Emerges after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys Coincident with gp140-Binding Antibodies and Is Effective against Neutralization-Resistant Viruses
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DOI：
10.1128/jvi.00313-11
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Letvin, Norman L.
中科院分区：
文献类型：
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作者：
Asmal, Mohammed;Sun, Yue;Letvin, Norman L.
抗体依赖细胞介导的病毒抑制(ADCVI)是一种很有吸引力的疫苗接种靶标，因为它既利用了获得性免疫反应的记忆特性，又利用了先天免疫反应的快速早期反应特性。ADCVI在疫苗策略中的有效利用将取决于对ADCVI在急性和慢性人类免疫缺陷病毒1型(HIV-1)感染期间的自然历史的了解。我们以猴免疫缺陷病毒(SIV)感染的恒河猴为模型，研究了ADCVI在感染早期的动力学，ADCVI在感染过程中的持久性，以及ADCVI对具有包膜突变的病毒的有效性，这些病毒具有已知的逃避抗体中和的能力。我们证明了ADCVI的发展，能够在感染后3周内将病毒复制抑制100倍，比形成类似效价的中和抗体反应早几周到几个月。ADCVI的出现与gp140结合抗体的出现是暂时的，在大多数动物中，ADCVI持续整个感染过程。从感染后后期分离的病毒高度进化的、抵抗血浆中和的病毒包膜仍然对ADCVI敏感，这表明介导ADCVI的抗体并不共享中和逃逸的表位决定因素。这些发现表明，尽管SIV在感染过程中具有变异和适应多种免疫压力的能力，但SIV包膜可能无法逃脱介导ADCVI的自身抗体的结合。
Antibody-dependent cell-mediated viral inhibition (ADCVI) is an attractive target for vaccination because it takes advantage of both the anamnestic properties of an adaptive immune response and the rapid early response characteristics of an innate immune response. Effective utilization of ADCVI in vaccine strategies will depend on an understanding of the natural history of ADCVI during acute and chronic human immunodeficiency virus type 1 (HIV-1) infection. We used the simian immunodeficiency virus (SIV)-infected rhesus monkey as a model to study the kinetics of ADCVI in early infection, the durability of ADCVI through the course of infection, and the effectiveness of ADCVI against viruses with envelope mutations that are known to confer escape from antibody neutralization. We demonstrate the development of ADCVI, capable of inhibiting viral replication 100-fold, within 3 weeks of infection, preceding the development of a comparable-titer neutralizing antibody response by weeks to months. The emergence of ADCVI was temporally associated with the emergence of gp140-binding antibodies, and in most animals, ADCVI persisted through the course of infection. Highly evolved viral envelopes from viruses isolated at late time points following infection that were resistant to plasma neutralization remained susceptible to ADCVI, suggesting that the epitope determinants of neutralization escape are not shared by antibodies that mediate ADCVI. These findings suggest that despite the ability of SIV to mutate and adapt to multiple immunologic pressures during the course of infection, SIV envelope may not escape the binding of autologous antibodies that mediate ADCVI.