Xu Ling, Pegu Amarendra, Rao Ercole, Doria-Rose Nicole, Beninga Jochen, McKee Krisha, Lord Dana M, Wei Ronnie R, Deng Gejing, Louder Mark, Schmidt Stephen D, Mankoff Zachary, Wu Lan, Asokan Mangaiarkarasi, Beil Christian, Lange Christian, Leuschner Wulf Dirk, Kruip Jochen, Sendak Rebecca, Kwon Young Do, Zhou Tongqing, Chen Xuejun, Bailer Robert T, Wang Keyun, Choe Misook, Tartaglia Lawrence J, Barouch Dan H, O'Dell Sijy, Todd John-Paul, Burton Dennis R, Roederer Mario, Connors Mark, Koup Richard A, Kwong Peter D, Yang Zhi-Yong, Mascola John R, Nabel Gary J
Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Science. 2017 Oct 6;358(6359):85-90. doi: 10.1126/science.aan8630. Epub 2017 Sep 20.
The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity.
由于病毒的基因多样性以及产生广泛中和抗体（bnAbs）的困难，开发一种有效的艾滋病疫苗一直具有挑战性。我们设计了三特异性抗体（Abs），使单个分子能够与三个独立的HIV-1包膜决定簇相互作用：CD4结合位点、膜近端外部区域（MPER）和V1V2聚糖位点。与任何先前描述的单一bnAb相比，三特异性抗体表现出更高的效力和广度，其药代动力学与人bnAbs相似，并且与单一bnAb不同，它能使非人灵长类动物对猿猴-人类免疫缺陷病毒（SHIVs）混合物产生完全免疫。因此，三特异性抗体构成了一个通过单一蛋白质作用于多个治疗靶点的平台，它们可能适用于治疗多种疾病，包括感染、癌症和自身免疫性疾病。
