| Title: |
Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform |
| Authors: |
Chevillard, Christopher; Amen, Axel; Besson, Solène; Hannani, Dalil; Bally, Isabelle; Dettling, Valentin; Gout, Evelyne; Moreau, Christophe; Buisson, Marlyse; Gallet, Salomé; Fenel, Daphna; Vassal-Stermann, Emilie; SCHOEHN, Guy; Poignard, Pascal; Dagher, Marie-Claire; Fender, Pascal |
| Contributors: |
Institut de biologie structurale (IBS - UMR 5075); Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ); VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ); Université Grenoble Alpes (UGA); GEFLUC Dauphiné-Savoie, Ligue contre le Cancer Comité Isère, Université Grenoble; Alpes IDEX Initiatives de Recherche Stratégiques and Fondation du Souffle-Fonds de recherche en santé respiratoire (FdS-FRSR); Région Auvergne Rhône-Alpes, AuRA; MEM; ISBG; ANR-20-COVI-0000,Flash Covid Cov Mime |
| Source: |
https://hal.univ-grenoble-alpes.fr/hal-03384730 ; 2021. |
| Publisher Information: |
HAL CCSD |
| Publication Year: |
2021 |
| Collection: |
Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| Subject Terms: |
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Structural Biology [q-bio.BM] |
| Description: |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity. |
| Document Type: |
report |
| Language: |
English |
| Relation: |
hal-03384730; https://hal.univ-grenoble-alpes.fr/hal-03384730; BIORXIV: 2021.09.13.460076 |
| DOI: |
10.1101/2021.09.13.460076 |
| Availability: |
https://hal.univ-grenoble-alpes.fr/hal-03384730; https://doi.org/10.1101/2021.09.13.460076 |
| Accession Number: |
edsbas.92C54778 |
| Database: |
BASE |