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Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants.

Authors :
Roland Züst
Shi-Hua Li
Xuping Xie
Sumathy Velumani
Melissa Chng
Ying-Xiu Toh
Jing Zou
Hongping Dong
Chao Shan
Jassia Pang
Cheng-Feng Qin
Evan W Newell
Pei-Yong Shi
Katja Fink
Source :
PLoS ONE, Vol 13, Iss 1, p e0189262 (2018)
Publication Year :
2018
Publisher :
Public Library of Science (PLoS), 2018.

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.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
13
Issue :
1
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.565c8ea8b41249f0903bf2b281241cf1
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0189262