鉴定一种与三种主要灵长类慢病毒属交叉反应的单克隆抗衣壳抗体。
Characterization of a monoclonal anti-capsid antibody that cross-reacts with three major primate lentivirus lineages.
机构信息
BIOQUAL, Inc., Rockville, MD 20850, USA.
出版信息
Virology. 2012 Jan 20;422(2):402-12. doi: 10.1016/j.virol.2011.11.003. Epub 2011 Dec 5.
Abstract
Mouse monoclonal antibodies with varying specificities against the Gag capsid of simian and human immunodeficiency virus (SIV/HIV) were generated by immunizing mice with whole inactivated SIVagmTYO-1. Monoclonal antibody AG3.0 showed the broadest reactivity recognizing the Gag capsid protein (p24-27) and Gag precursors p38, p55, and p150 of HIV-1, HIV-2, SIVmac, and SIVagm. Using overlapping peptides, the AG3.0 epitope was mapped in capsid to a sequence (SPRTLNA) conserved among HIV-1, HIV-2, SIVrcm, SIVsm/mac, and SIVagm related viruses. Because of its broad cross-reactivity, AG3.0 was used to develop an antigen capture assay with a lower detection limit of 100 pg/ml HIV-1 Gag p24. Interestingly, AG3.0 was found to have a faster binding on/off rate for SIVagmVer and SIVmac Gag than for SIVagmSab Gag, possibly due to differences outside the SPRTLNA motif. In addition, the ribonucleic acid (RNA) coding for AG3.0 was sequenced to facilitate the development of humanized monoclonal antibodies.
摘要
通过用全长灭活的 SIVagmTYO-1 免疫小鼠，产生了针对灵长类和人类免疫缺陷病毒（SIV/HIV）衣壳的具有不同特异性的小鼠单克隆抗体。单克隆抗体 AG3.0 表现出最广泛的反应性，可识别 HIV-1、HIV-2、SIVmac 和 SIVagm 的 Gag 衣壳蛋白（p24-27）和 Gag 前体 p38、p55 和 p150。使用重叠肽，AG3.0 表位在衣壳中被映射到 HIV-1、HIV-2、SIVrcm、SIVsm/mac 和 SIVagm 相关病毒之间保守的序列（SPRTLNA）上。由于其广泛的交叉反应性，AG3.0 被用于开发一种抗原捕获测定法，其对 HIV-1 Gag p24 的检测下限为 100 pg/ml。有趣的是，AG3.0 对 SIVagmVer 和 SIVmac Gag 的结合/解离速度比 SIVagmSab Gag 更快，这可能是由于 SPRTLNA 基序之外的差异所致。此外，对编码 AG3.0 的 RNA 进行了测序，以促进人源化单克隆抗体的开发。
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