Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity.
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Cytomegalovirus
/ immunology
Cytomegalovirus Infections
/ immunology
Cytomegalovirus Vaccines
/ immunology
Female
Humans
Mice
Mice, Inbred BALB C
Nanoparticles
Vaccines, Subunit
/ immunology
Viral Envelope Proteins
/ immunology
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
02
09
2020
accepted:
16
11
2020
revised:
08
01
2021
pubmed:
29
12
2020
medline:
23
1
2021
entrez:
28
12
2020
Statut:
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.
Identifiants
pubmed: 33370407
doi: 10.1371/journal.ppat.1009169
pii: PPATHOGENS-D-20-01960
pmc: PMC7794029
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Cytomegalovirus Vaccines
0
Vaccines, Subunit
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009169Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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