Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants.
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 effica...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5751980?pdf=render |
| _version_ | 1818267027275513856 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Roland Züst |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T20:16:04Z |
| format | Article |
| id | doaj.art-565c8ea8b41249f0903bf2b281241cf1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T20:16:04Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-565c8ea8b41249f0903bf2b281241cf12022-12-22T00:13:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e018926210.1371/journal.pone.0189262Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants.Roland ZüstShi-Hua LiXuping XieSumathy VelumaniMelissa ChngYing-Xiu TohJing ZouHongping DongChao ShanJassia PangCheng-Feng QinEvan W NewellPei-Yong ShiKatja FinkDengue 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.http://europepmc.org/articles/PMC5751980?pdf=render |
| spellingShingle | 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 Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants. PLoS ONE |
| title | Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants. |
| title_full | Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants. |
| title_fullStr | Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants. |
| title_full_unstemmed | Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants. |
| title_short | Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants. |
| title_sort | characterization of a candidate tetravalent vaccine based on 2 o methyltransferase mutants |
| url | http://europepmc.org/articles/PMC5751980?pdf=render |
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