Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity.
Détails
Télécharger: 33370407_BIB_711970C96BE8.pdf (2647.02 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_711970C96BE8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity.
Périodique
PLoS pathogens
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
12/2020
Peer-reviewed
Oui
Editeur⸱rice scientifique
Schleiss Mark
Volume
16
Numéro
12
Pages
e1009169
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Human cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable efforts in vaccine development, HCMV infection still represents an unmet clinical need. In recent phase II trials, a MF59-adjuvanted gB vaccine showed only modest efficacy in preventing infection. These findings might be attributed to low level of antibodies (Abs) with a neutralizing activity induced by this vaccine. Here, we analyzed the immunogenicity of each gB antigenic domain (AD) and demonstrated that domain I of gB (AD5) is the main target of HCMV neutralizing antibodies. Furthermore, we designed, characterized and evaluated immunogenic responses to two different nanoparticles displaying a trimeric AD5 antigen. We showed that mice immunization with nanoparticles induces sera neutralization titers up to 100-fold higher compared to those obtained with the gB extracellular domain (gBECD). Collectively, these results illustrate with a medically relevant example the advantages of using a general approach combining antigen discovery, protein engineering and scaffold presentation for modern development of subunit vaccines against complex pathogens.
Mots-clé
Immunology, Genetics, Molecular Biology, Microbiology, Parasitology, Virology
Pubmed
Web of science
Site de l'éditeur
Open Access
Oui
Création de la notice
02/01/2021 21:50
Dernière modification de la notice
21/11/2022 9:30