Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity.

Details

Ressource 1Download: 33370407_BIB_711970C96BE8.pdf (2647.02 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_711970C96BE8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity.
Journal
PLoS pathogens
Author(s)
Perotti M., Marcandalli J., Demurtas D., Sallusto F., Perez L.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
12/2020
Peer-reviewed
Oui
Editor
Schleiss Mark
Volume
16
Number
12
Pages
e1009169
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Immunology, Genetics, Molecular Biology, Microbiology, Parasitology, Virology
Pubmed
Web of science
Open Access
Yes
Create date
02/01/2021 21:50
Last modification date
30/04/2021 7:11
Usage data