期刊
CELL
卷 176, 期 6, 页码 1420-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.01.046
关键词
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资金
- Bill and Melinda Gates Foundation [OPP1120319, OPP1126258, OPP1162875]
- state of Washington
- Howard Hughes Medical Institute
- Netherlands Organization for Scientific Research (NWO) [Rubicon 019.2015.2.310.006]
- European Molecular Biology Organisation (EMBO) [ALTF 933-2015]
- Swedish Research Council [Vetenskapsradet 2015-02608]
- Karolinska Institutet
- NIAID [HHSN272201700059C]
- NIGMS [R01GM120553]
- Pew Biomedical Scholars Award
- Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund
- Bill and Melinda Gates Foundation [OPP1162875, OPP1120319, OPP1126258] Funding Source: Bill and Melinda Gates Foundation
Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses similar to 10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design.
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