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dc.contributor.author
Perotti, Michela
dc.contributor.author
Marcandalli, Jessica
dc.contributor.author
Demurtas, Davide
dc.contributor.author
Sallusto, Federica
dc.contributor.author
Perez, Laurent
dc.date.accessioned
2021-01-28T16:22:51Z
dc.date.available
2021-01-08T03:45:30Z
dc.date.available
2021-01-08T11:36:33Z
dc.date.available
2021-01-28T16:22:51Z
dc.date.issued
2020-12-28
dc.identifier.issn
1553-7374
dc.identifier.issn
1553-7366
dc.identifier.other
10.1371/journal.ppat.1009169
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/460387
dc.identifier.doi
10.3929/ethz-b-000460387
dc.description.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PLOS
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS Pathogens
ethz.journal.volume
16
en_US
ethz.journal.issue
12
en_US
ethz.journal.abbreviated
PLoS Pathog
ethz.pages.start
e1009169
en_US
ethz.size
24 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Lawrence, KS
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::09604 - Sallusto, Federica / Sallusto, Federica
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::09604 - Sallusto, Federica / Sallusto, Federica
ethz.date.deposited
2021-01-08T03:45:37Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-01-28T16:23:01Z
ethz.rosetta.lastUpdated
2024-02-02T12:59:51Z
ethz.rosetta.versionExported
true
ethz.COinS
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