Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1003521
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dc.titleRational Design of a Live Attenuated Dengue Vaccine: 2?-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques
dc.contributor.authorZüst R.
dc.contributor.authorDong H.
dc.contributor.authorLi X.-F.
dc.contributor.authorChang D.C.
dc.contributor.authorZhang B.
dc.contributor.authorBalakrishnan T.
dc.contributor.authorToh Y.-X.
dc.contributor.authorJiang T.
dc.contributor.authorLi S.-H.
dc.contributor.authorDeng Y.-Q.
dc.contributor.authorEllis B.R.
dc.contributor.authorEllis E.M.
dc.contributor.authorPoidinger M.
dc.contributor.authorZolezzi F.
dc.contributor.authorQin C.-F.
dc.contributor.authorShi P.-Y.
dc.contributor.authorFink K.
dc.date.accessioned2019-11-06T09:26:07Z
dc.date.available2019-11-06T09:26:07Z
dc.date.issued2013
dc.identifier.citationZüst R., Dong H., Li X.-F., Chang D.C., Zhang B., Balakrishnan T., Toh Y.-X., Jiang T., Li S.-H., Deng Y.-Q., Ellis B.R., Ellis E.M., Poidinger M., Zolezzi F., Qin C.-F., Shi P.-Y., Fink K. (2013). Rational Design of a Live Attenuated Dengue Vaccine: 2?-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques. PLoS Pathogens 9 (8) : e1003521. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1003521
dc.identifier.issn15537366
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161619
dc.description.abstractDengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2?-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2?-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2?-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response. © 2013 Züst et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subject2 O methyltransferase
dc.subjectdengue vaccine
dc.subjectimmunoglobulin G
dc.subjectinterferon
dc.subjectneutralizing antibody
dc.subjectunclassified drug
dc.subjectvirus envelope protein
dc.subjectvirus enzyme
dc.subjectvirus RNA
dc.subjectdengue vaccine
dc.subjectinterferon
dc.subjectlive vaccine
dc.subjectmethyltransferase
dc.subjectRNA 2'-O-methyltransferase
dc.subjectadaptive immunity
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantibody dependent enhancement
dc.subjectarticle
dc.subjectCD8+ T lymphocyte
dc.subjectcell strain BHK
dc.subjectcell strain HEK293
dc.subjectcontrolled study
dc.subjectdengue
dc.subjectDengue virus 1
dc.subjectDengue virus 2
dc.subjectenzyme linked immunosorbent assay
dc.subjectfemale
dc.subjectflow cytometry
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmunofluorescence
dc.subjectinnate immunity
dc.subjectmale
dc.subjectmethylation
dc.subjectmosquito
dc.subjectmouse
dc.subjectnonhuman
dc.subjectreverse transcription polymerase chain reaction
dc.subjectrhesus monkey
dc.subjectseroconversion
dc.subjectviremia
dc.subjectvirus isolation
dc.subjectvirus mutant
dc.subjectvirus neutralization
dc.subjectvirus transmission
dc.subjectanimal
dc.subjectdengue
dc.subjectDengue virus
dc.subjectenzymology
dc.subjectgenetics
dc.subjecthamster
dc.subjectHEK293 cell line
dc.subjectimmunology
dc.subjectmutant mouse strain
dc.subjectmutation
dc.subjectAnimals
dc.subjectCricetinae
dc.subjectDengue
dc.subjectDengue Vaccines
dc.subjectDengue Virus
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectInterferon Type I
dc.subjectMacaca mulatta
dc.subjectMethyltransferases
dc.subjectMice
dc.subjectMice, Mutant Strains
dc.subjectMutation
dc.subjectVaccines, Attenuated
dc.typeArticle
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.ppat.1003521
dc.description.sourcetitlePLoS Pathogens
dc.description.volume9
dc.description.issue8
dc.description.pagee1003521
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