期刊
MOLECULAR THERAPY
卷 30, 期 5, 页码 1913-1925出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2022.02.011
关键词
-
资金
- CNRS Prematuration program
- ANRFlash COVID
- Region Auvergne-Rhone-Alpes, AuRA
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [682286]
- GEFLUC DauphineSavoie
- Ligue contre le Cancer Comite Isere
- Universite Grenoble Alpes IDEX Initiatives de Recherche Strategiques
- Fondation du Souffle-Fonds de recherche en sante respiratoire (FdS-FRSR)
- FRISBI [ANR-10-INBS-05-02]
- University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS [ANR-17-EURE-0003]
- Auvergne-Rhone-Alpes Region
- Fondation Recherche Medicale (FRM)
- fonds FEDER
- GIS-Infrastructures en Biologie Sante et Agronomie (IBISA)
In this study, a previously designed ADDomer VLP platform was adapted to display multimeric array of large antigens using the SpyTag/SpyCatcher system. By decorating the newly designed VLP with glycosylated receptor binding domain of SARS-CoV-2, significant specific humoral response and strong neutralization titers were induced, surpassing those of COVID-19 convalescent patients.
Virus-like particles (VLPs) are highly suited platforms for protein-based vaccines. In the present work, we adapted a previously designed non-infectious adenovirus-inspired 60-mer dodecahedric VLP (ADDomer) to display a multimeric array of large antigens through a SpyTag/SpyCatcher system. To validate the platform as a potential COVID-19 vaccine approach, we decorated the newly designed VLP with the glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryoelectron microscopy structure revealed that up to 60 copies of this antigenic domain could be bound on a single ADDomer particle, with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated VLPs already showed a significant specific humoral response following prime vaccination, greatly reinforced by a single boost. Neutralization assays with SARS-CoV-2 spike pseudo-typed virus demonstrated the elicitation of strong neutralization titers, superior to those of COVID-19 convalescent patients. Notably, the presence of pre-existing immunity against the adenoviral-derived particles did not hamper the immune response against the antigen displayed on its surface. This plug and play vaccine platform represents a promising new highly versatile tool to combat emergent pathogens.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据