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https://doi.org/10.1038/s41467-018-03337-2
Title: | A systematic approach to the development of a safe live attenuated Zika vaccine | Authors: | Kwek, S.S Watanabe, S Chan, K.R Ong, E.Z Tan, H.C Ng, W.C Nguyen, M.T.X Gan, E.S Zhang, S.L Chan, K.W.K Tan, J.H Sessions, O.M Manuel, M Pompon, J Chua, C Hazirah, S Tryggvason, K Vasudevan, S.G Ooi, E.E |
Keywords: | interferon regulatory factor 3 live vaccine Zika virus vaccine live vaccine virus vaccine cell immunity rodent strategic approach vaccine vertical transmission yellow fever Zika virus disease adult animal cell animal experiment animal model animal tissue Article B lymphocyte controlled study dendritic cell drug efficacy drug mechanism drug safety embryo female fetus gene activation genetic variability genomic instability human human cell in vitro propagation infection risk innate immunity male mouse mouse model next generation sequencing nonhuman single nucleotide polymorphism T lymphocyte umbilical vein endothelial cell vaccine immunogenicity Vero cell line vertical transmission virus culture virus mutation virus plaque virus transmission whole genome sequencing wild type Zika fever Zika virus Aedes animal evaluation study genetics growth, development and aging immunological technique immunology virology Zika fever Flavivirus Human immunodeficiency virus 1 Zika virus Aedes Animals Dendritic Cells Humans Immunologic Techniques Mice Vaccines, Attenuated Viral Vaccines Zika Virus Zika Virus Infection |
Issue Date: | 2018 | Publisher: | Nature Publishing Group | Citation: | Kwek, S.S, Watanabe, S, Chan, K.R, Ong, E.Z, Tan, H.C, Ng, W.C, Nguyen, M.T.X, Gan, E.S, Zhang, S.L, Chan, K.W.K, Tan, J.H, Sessions, O.M, Manuel, M, Pompon, J, Chua, C, Hazirah, S, Tryggvason, K, Vasudevan, S.G, Ooi, E.E (2018). A systematic approach to the development of a safe live attenuated Zika vaccine. Nature Communications 9 (1) : 1031. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-018-03337-2 | Abstract: | Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV. © 2018 The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/174234 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-018-03337-2 |
Appears in Collections: | Elements Staff Publications |
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