Please use this identifier to cite or link to this item:
https://doi.org/10.1371/journal.ppat.1003521
DC Field | Value | |
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dc.title | Rational Design of a Live Attenuated Dengue Vaccine: 2?-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques | |
dc.contributor.author | Züst R. | |
dc.contributor.author | Dong H. | |
dc.contributor.author | Li X.-F. | |
dc.contributor.author | Chang D.C. | |
dc.contributor.author | Zhang B. | |
dc.contributor.author | Balakrishnan T. | |
dc.contributor.author | Toh Y.-X. | |
dc.contributor.author | Jiang T. | |
dc.contributor.author | Li S.-H. | |
dc.contributor.author | Deng Y.-Q. | |
dc.contributor.author | Ellis B.R. | |
dc.contributor.author | Ellis E.M. | |
dc.contributor.author | Poidinger M. | |
dc.contributor.author | Zolezzi F. | |
dc.contributor.author | Qin C.-F. | |
dc.contributor.author | Shi P.-Y. | |
dc.contributor.author | Fink K. | |
dc.date.accessioned | 2019-11-06T09:26:07Z | |
dc.date.available | 2019-11-06T09:26:07Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Züst 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.issn | 15537366 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/161619 | |
dc.description.abstract | Dengue 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.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20191101 | |
dc.subject | 2 O methyltransferase | |
dc.subject | dengue vaccine | |
dc.subject | immunoglobulin G | |
dc.subject | interferon | |
dc.subject | neutralizing antibody | |
dc.subject | unclassified drug | |
dc.subject | virus envelope protein | |
dc.subject | virus enzyme | |
dc.subject | virus RNA | |
dc.subject | dengue vaccine | |
dc.subject | interferon | |
dc.subject | live vaccine | |
dc.subject | methyltransferase | |
dc.subject | RNA 2'-O-methyltransferase | |
dc.subject | adaptive immunity | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | antibody dependent enhancement | |
dc.subject | article | |
dc.subject | CD8+ T lymphocyte | |
dc.subject | cell strain BHK | |
dc.subject | cell strain HEK293 | |
dc.subject | controlled study | |
dc.subject | dengue | |
dc.subject | Dengue virus 1 | |
dc.subject | Dengue virus 2 | |
dc.subject | enzyme linked immunosorbent assay | |
dc.subject | female | |
dc.subject | flow cytometry | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | immunofluorescence | |
dc.subject | innate immunity | |
dc.subject | male | |
dc.subject | methylation | |
dc.subject | mosquito | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | reverse transcription polymerase chain reaction | |
dc.subject | rhesus monkey | |
dc.subject | seroconversion | |
dc.subject | viremia | |
dc.subject | virus isolation | |
dc.subject | virus mutant | |
dc.subject | virus neutralization | |
dc.subject | virus transmission | |
dc.subject | animal | |
dc.subject | dengue | |
dc.subject | Dengue virus | |
dc.subject | enzymology | |
dc.subject | genetics | |
dc.subject | hamster | |
dc.subject | HEK293 cell line | |
dc.subject | immunology | |
dc.subject | mutant mouse strain | |
dc.subject | mutation | |
dc.subject | Animals | |
dc.subject | Cricetinae | |
dc.subject | Dengue | |
dc.subject | Dengue Vaccines | |
dc.subject | Dengue Virus | |
dc.subject | HEK293 Cells | |
dc.subject | Humans | |
dc.subject | Interferon Type I | |
dc.subject | Macaca mulatta | |
dc.subject | Methyltransferases | |
dc.subject | Mice | |
dc.subject | Mice, Mutant Strains | |
dc.subject | Mutation | |
dc.subject | Vaccines, Attenuated | |
dc.type | Article | |
dc.contributor.department | DEPT OF BIOLOGICAL SCIENCES | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1371/journal.ppat.1003521 | |
dc.description.sourcetitle | PLoS Pathogens | |
dc.description.volume | 9 | |
dc.description.issue | 8 | |
dc.description.page | e1003521 | |
Appears in Collections: | Elements Staff Publications |
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