三种特异性大致中和性HIV抗体在中提供强大的SHIV保护
Ling Xu1, Amarendra Pegu2, Ercole Rao1
1Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|September 22, 2017
概括
研究人员设计了针对HIV-1病毒多个部位的新型三种特异性抗体 (Abs). 在动物模型中提供完整的免疫力, 为新的HIV治疗铺平了道路.
科学领域:
- 免疫学和病毒学
- 生物技术和抗体工程
背景情况:
- 开发有效的艾滋病疫苗受到HIV-1的遗传多样性和产生广泛中和抗体 (bnAbs) 的挑战的阻碍.
- 现有的单一bnAbs在实现对HIV-1的广泛和有效中和方面存在局限性.
研究的目的:
- 设计能够同时向多个保存的HIV-1包膜决定因素的新型三特异性抗体 (Abs).
- 为了评估这些工程三种特异性的Abs的功效,范围,药理动力学和体内疗效.
主要方法:
- 设计的三种特异性抗体可结合到三种不同的HIV-1包膜部位:CD4结合部位,膜近接外部区域 (MPER) 和V1V2糖部位.
- 对各种HIV-1株的抗体强度和范围进行了评估.
- 在相关模型中评估药理动力学,并在非人类灵长类动物中使用猿人免疫缺陷病毒 (SHIV) 挑战测试了体内疗效.
主要成果:
- 与之前描述的单个bnAbs相比,Trispecific Abs的强度和范围显著更高.
- 工程Abs表现出与人类bnAbs相似的药物动力学特征.
- 在非人类灵长类动物中实现了对SHIV挑战的完全免疫力,这种结果在单个bnAbs中没有出现.
结论:
- 三种特异性抗体代表了与单个分子实体接触多个治疗点的有希望的平台.
- 这种方法可能为开发有效的HIV-1和潜在的其他疾病,如癌症和自身免疫性疾病提供一个可行的策略.
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