| Literature DB >> 28931639 |
Ling Xu1, Amarendra Pegu2, Ercole Rao1, Nicole Doria-Rose2, Jochen Beninga1, Krisha McKee2, Dana M Lord1, Ronnie R Wei1, Gejing Deng1, Mark Louder2, Stephen D Schmidt2, Zachary Mankoff2, Lan Wu1, Mangaiarkarasi Asokan2, Christian Beil1, Christian Lange1, Wulf Dirk Leuschner1, Jochen Kruip1, Rebecca Sendak1, Young Do Kwon2, Tongqing Zhou2, Xuejun Chen2, Robert T Bailer2, Keyun Wang2, Misook Choe2, Lawrence J Tartaglia3,4, Dan H Barouch3,4, Sijy O'Dell2, John-Paul Todd2, Dennis R Burton4,5, Mario Roederer2, Mark Connors6, Richard A Koup2, Peter D Kwong2, Zhi-Yong Yang1, John R Mascola7, Gary J Nabel8.
Abstract
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.Entities:
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Year: 2017 PMID： 28931639 PMCID： PMC5978417 DOI： 10.1126/science.aan8630
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728