@article{ca6e1358fd9a4a32a5d8469d584e144e,
title = "Characterization of a candidate tetravalent vaccine based on 2{\textquoteright}-O-methyltransferase mutants",
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{\textquoteright}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{\textquoteright}-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{\textquoteright}-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{\textquoteright}-O-methyltransferase mutant viruses as a safe, tetravalent, non-chimeric dengue vaccine.",
author = "Roland Z{\"u}st and Li, {Shi Hua} and Xuping Xie and Sumathy Velumani and Melissa Chng and Toh, {Ying Xiu} and Jing Zou and Hongping Dong and Chao Shan and Jassia Pang and Qin, {Cheng Feng} and Newell, {Evan W.} and Shi, {Pei Yong} and Katja Fink",
note = "Funding Information: KF received funding from the ASTAR Translational Infectious Diseases Research Program IAF311003. P.Y.S. lab was supported by University of Texas Medical Branch (UTMB) startup award, University of Texas STARs Award, CDC grant for the Western Gulf Center of Excellence for Vector-Borne Diseases, Pan American Health Organization grant SCON2016-01353, the Kleberg Foundation Award, UTMB CTSA UL1TR-001439, and NIH grant AI127744.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Jun Jia Koh, Jan Irving Antonio Bibay, Rahmat Hidayat Bin Jemaah, Timothy Chua, and Zhang Wei for technical assistance with the NHP study, and Hannes Hentze for reviewing the NHP report. Publisher Copyright: {\textcopyright} 2018 Z{\"u}st 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.",
year = "2018",
month = jan,
doi = "10.1371/journal.pone.0189262",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",
}