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Mutating chikungunya virus non-structural protein produces potent live-attenuated vaccine candidate.
- Source :
-
EMBO molecular medicine [EMBO Mol Med] 2019 Jun; Vol. 11 (6). - Publication Year :
- 2019
-
Abstract
- 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.<br /> (© 2019 Agency for Science, Technology and Research (A*STAR). Published under the terms of the CC BY 4.0 license.)
- Subjects :
- Animals
Chikungunya Fever genetics
Chikungunya Fever immunology
Chlorocebus aethiops
Mice
Vaccines, Attenuated genetics
Vaccines, Attenuated immunology
Vero Cells
Chikungunya Fever prevention & control
Chikungunya virus genetics
Chikungunya virus immunology
Mutation
Viral Nonstructural Proteins genetics
Viral Nonstructural Proteins immunology
Viral Vaccines genetics
Viral Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1757-4684
- Volume :
- 11
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- EMBO molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31015278
- Full Text :
- https://doi.org/10.15252/emmm.201810092