Mutating chikungunya virus non-structural protein produces potent live-attenuated vaccine candidate
© 2019 Agency for Science, Technology and Research (A*STAR). Published under the terms of the CC BY 4.0 license..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
EMBO molecular medicine - 11(2019), 6 vom: 23. Juni |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chan, Yi-Hao [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 24.04.2020 Date Revised 24.04.2020 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.15252/emmm.201810092 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM296354864 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM296354864 | ||
| 003 | DE-627 | ||
| 005 | 20231225085647.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.15252/emmm.201810092 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0987.xml |
| 035 | |a (DE-627)NLM296354864 | ||
| 035 | |a (NLM)31015278 | ||
| 035 | |a (PII)e10092 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chan, Yi-Hao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mutating chikungunya virus non-structural protein produces potent live-attenuated vaccine candidate |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.04.2020 | ||
| 500 | |a Date Revised 24.04.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 Agency for Science, Technology and Research (A*STAR). Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a chikungunya | |
| 650 | 4 | |a live‐attenuated vaccine | |
| 650 | 4 | |a mutation | |
| 650 | 4 | |a neutralizing antibody | |
| 650 | 4 | |a non‐structural protein | |
| 650 | 7 | |a Vaccines, Attenuated |2 NLM | |
| 650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
| 650 | 7 | |a Viral Vaccines |2 NLM | |
| 700 | 1 | |a Teo, Teck-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Utt, Age |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Jeslin Jl |e verfasserin |4 aut | |
| 700 | 1 | |a Amrun, Siti Naqiah |e verfasserin |4 aut | |
| 700 | 1 | |a Abu Bakar, Farhana |e verfasserin |4 aut | |
| 700 | 1 | |a Yee, Wearn-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Becht, Etienne |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Cheryl Yi-Pin |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Bernett |e verfasserin |4 aut | |
| 700 | 1 | |a Rajarethinam, Ravisankar |e verfasserin |4 aut | |
| 700 | 1 | |a Newell, Evan |e verfasserin |4 aut | |
| 700 | 1 | |a Merits, Andres |e verfasserin |4 aut | |
| 700 | 1 | |a Carissimo, Guillaume |e verfasserin |4 aut | |
| 700 | 1 | |a Lum, Fok-Moon |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Lisa Fp |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t EMBO molecular medicine |d 2009 |g 11(2019), 6 vom: 23. Juni |w (DE-627)NLM192618962 |x 1757-4684 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2019 |g number:6 |g day:23 |g month:06 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.15252/emmm.201810092 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2019 |e 6 |b 23 |c 06 | ||