Open AccessMutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate
Author(s) -
Chan YiHao,
Teo TeckHui,
Utt Age,
Tan Jeslin JL,
Amrun Siti Naqiah,
Abu Bakar Farhana,
Yee WearnXin,
Becht Etienne,
Lee Cheryl YiPin,
Lee Bernett,
Rajarethinam Ravisankar,
Newell Evan,
Merits Andres,
Carissimo Guillaume,
Lum FokMoon,
Ng Lisa FP
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201810092
Subject(s) - chikungunya , virology , virus , attenuated vaccine , chikungunya fever , alphavirus , biology , genetics , gene , virulence
Currently, there are no commercially available live‐attenuated vaccines against chikungunya virus ( CHIKV ). Here, CHIKV s 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.