Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0189262
Title: Characterization of a candidate tetravalent vaccine based on 2’-O-methyltransferase mutants
Authors: Züst R.
Li S.-H.
Xie X.
Velumani S.
Chng M.
Toh Y.-X.
Zou J.
Dong H.
Shan C.
Pang J.
Qin C.-F.
Newell E.W.
Shi P.-Y. 
Fink K.
Keywords: dengue vaccine
interferon
tetravalent vaccine
unclassified drug
dengue vaccine
methyltransferase
neutralizing antibody
adaptive immunity
animal experiment
animal model
animal tissue
Article
controlled study
cytokine response
dengue
Dengue virus 1
Dengue virus 2
drug efficacy
female
immunogenicity
infection prevention
innate immunity
Macaca fascicularis
mouse
nonhuman
outcome assessment
serotype
vaccination
animal
cell line
Dengue virus
enzyme linked immunosorbent assay
genetics
human
immunology
male
mutation
Animals
Antibodies, Neutralizing
Cell Line
Dengue Vaccines
Dengue Virus
Enzyme-Linked Immunosorbent Assay
Female
Humans
Macaca fascicularis
Male
Methyltransferases
Mice
Mutation
Issue Date: 2018
Citation: Züst R., Li S.-H., Xie X., Velumani S., Chng M., Toh Y.-X., Zou J., Dong H., Shan C., Pang J., Qin C.-F., Newell E.W., Shi P.-Y., Fink K. (2018). Characterization of a candidate tetravalent vaccine based on 2’-O-methyltransferase mutants. PLoS ONE 13 (1) : e0189262. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0189262
Rights: Attribution 4.0 International
Abstract: Dengue virus (DENV) is one of the most widespread arboviruses. The four DENV serotypes infect about 400 million people every year, causing 96 million clinical dengue cases, of which approximately 500’000 are severe and potentially life-threatening. The only licensed vaccine has a limited efficacy and is only recommended in regions with high endemicity. We previously reported that 2’-O-methyltransferase mutations in DENV-1 and DENV-2 block their capacity to inhibit type I IFNs and render the viruses attenuated in vivo, making them amenable as vaccine strains; here we apply this strategy to all four DENV serotypes to generate a tetravalent, non-chimeric live-attenuated dengue vaccine. 2’-O-methyltransferase mutants of all four serotypes are highly sensitive to type I IFN inhibition in human cells. The tetravalent formulation is attenuated and immunogenic in mice and cynomolgus macaques and elicits a response that protects from virus challenge. These results show the potential of 2’-O-methyltransferase mutant viruses as a safe, tetravalent, non-chimeric dengue vaccine. © 2018 Züst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161242
ISSN: 19326203
DOI: 10.1371/journal.pone.0189262
Rights: Attribution 4.0 International
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