Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 11 2022
25 11 2022
Historique:
received:
24
02
2022
accepted:
14
11
2022
entrez:
26
11
2022
pubmed:
27
11
2022
medline:
30
11
2022
Statut:
epublish
Résumé
Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization.
Identifiants
pubmed: 36434005
doi: 10.1038/s41467-022-34961-8
pii: 10.1038/s41467-022-34961-8
pmc: PMC9700739
doi:
Substances chimiques
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
Viral Envelope Proteins
0
Hepatitis C Antibodies
0
Glycoproteins
0
Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7271Subventions
Organisme : Bill & Melinda Gates Foundation
ID : INV-008352
Pays : United States
Informations de copyright
© 2022. The Author(s).
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