作者
Linling He, Sonu Kumar, Joel D Allen, Deli Huang, Xiaohe Lin, Colin J Mann, Karen L Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B Ward, David Nemazee, Dennis R Burton, Ian A Wilson, Jiang Zhu
发表日期
2018/11/21
期刊
Science advances
卷号
4
期号
11
页码范围
eaau6769
出版商
American Association for the Advancement of Science
简介
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41ECTO) is the main source of envelope metastability by replacing wild-type gp41ECTO with BG505 gp41ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41ECTO-swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41ECTO-swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41ECTO suggest an evolutionary root of metastability. The gp41ECTO-stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation …
学术搜索中的文章
L He, S Kumar, JD Allen, D Huang, X Lin, CJ Mann… - Science advances, 2018