Mutating chikungunya virus non-structural protein produces potent live-attenuated vaccine candidate.
chikungunya
live‐attenuated vaccine
mutation
neutralizing antibody
non‐structural protein
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
pubmed:
25
4
2019
medline:
25
4
2020
entrez:
25
4
2019
Statut:
ppublish
Résumé
Currently, there are no commercially available live-attenuated vaccines against chikungunya virus (CHIKV). Here, CHIKVs with mutations in non-structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. R532H mutation in nsP1 caused reduced infectivity in mouse tail fibroblasts but an enhanced type-I IFN response compared to WT-CHIKV Adult mice infected with this nsP-mutant exhibited a mild joint phenotype with low-level viremia that rapidly cleared. Mechanistically, ingenuity pathway analyses revealed a tilt in the anti-inflammatory IL-10 versus pro-inflammatory IL-1β and IL-18 balance during CHIKV nsP-mutant infection that modified acute antiviral and cell signaling canonical pathways. Challenging CHIKV nsP-mutant-infected mice with WT-CHIKV or the closely related O'nyong-nyong virus resulted in no detectable viremia, observable joint inflammation, or damage. Challenged mice showed high antibody titers with efficient neutralizing capacity, indicative of immunological memory. Manipulating molecular processes that govern CHIKV replication could lead to plausible vaccine candidates against alphavirus infection.
Identifiants
pubmed: 31015278
pii: emmm.201810092
doi: 10.15252/emmm.201810092
pmc: PMC6554673
pii:
doi:
Substances chimiques
Vaccines, Attenuated
0
Viral Nonstructural Proteins
0
Viral Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019 Agency for Science, Technology and Research (A*STAR). Published under the terms of the CC BY 4.0 license.
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