Zika Virus-Like Particles Bearing a Covalent Dimer of Envelope Protein Protect Mice from Lethal Challenge.
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Antibody-Dependent Enhancement
Cross Protection
Mice
Protein Conformation
Protein Multimerization
Vaccination
Vaccines, Virus-Like Particle
/ immunology
Viral Envelope Proteins
/ chemistry
Viral Vaccines
/ immunology
Zika Virus
/ classification
Zika Virus Infection
/ prevention & control
Zika
neutralizing antibodies
vaccine
virus-like particles
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
09 12 2020
09 12 2020
Historique:
received:
14
07
2020
accepted:
03
10
2020
pubmed:
9
10
2020
medline:
17
3
2021
entrez:
8
10
2020
Statut:
epublish
Résumé
Zika virus (ZIKV) envelope (E) protein is the major target of neutralizing antibodies in infected hosts and thus represents a candidate of interest for vaccine design. However, a major concern in the development of vaccines against ZIKV and the related dengue virus is the induction of cross-reactive poorly neutralizing antibodies that can cause antibody-dependent enhancement (ADE) of infection. This risk necessitates particular care in vaccine design. Specifically, the engineered immunogens should have their cross-reactive epitopes masked, and they should be optimized for eliciting virus-specific strongly neutralizing antibodies upon vaccination. Here, we developed ZIKV subunit- and virus-like particle (VLP)-based vaccines displaying E in its wild-type form or E locked in a covalently linked dimeric (cvD) conformation to enhance the exposure of E dimers to the immune system. Compared with their wild-type derivatives, cvD immunogens elicited antibodies with a higher capacity to neutralize virus infection in cultured cells. More importantly, these immunogens protected animals from lethal challenge with both the African and Asian lineages of ZIKV, impairing virus dissemination to brain and sexual organs. Moreover, the locked conformation of E reduced the exposure of epitopes recognized by cross-reactive antibodies and therefore showed a lower potential to induce ADE
Identifiants
pubmed: 33028720
pii: JVI.01415-20
doi: 10.1128/JVI.01415-20
pmc: PMC7737734
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Vaccines, Virus-Like Particle
0
Viral Envelope Proteins
0
Viral Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : G0801822
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U130184144
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/8
Pays : United Kingdom
Informations de copyright
Copyright © 2020 De Lorenzo et al.
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