Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells

• DOI: 10.1073/pnas.2010320117
• Publication Date: 2020-07-21T00:25:36Z
• Authors: Magnus A. G. Hoff...; Yotam Bar-On; Zhi Yang; Harry B. Gristick; Priyanthi N. P. G...; Jost Vielmetter; Michel C. Nussenz...; Pamela J. Bjorkman
• Keywords: Avidity; Entry inhibitor

Significance The ability of HIV-1 to rapidly develop resistance against various therapeutics remains a roadblock finding cure. Here we propose that nanoparticle-based mimic target cells by presenting clusters CD4, the receptor, could prevent effective viral escape. We show CD4 multimerization on nanoparticle dramatically enhanced neutralization potency and breadth compared with conventional CD4-based reagents present only one or two copies CD4. nanoparticles neutralized range diverse strains, including patient isolates resistant multiple broadly neutralizing antibodies. This work describes new therapeutic direction exploits need bind cells, thus warranting further investigation for potential development