Characterization of a candidate tetravalent vaccine based on 2’-O-methyltransferase mutants

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 500’000 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.

Original languageEnglish (US)
Article numbere0189262
JournalPLoS One
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

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Dengue virus
Dengue Virus
methyltransferases
Methyltransferases
Viruses
Vaccines
dengue
vaccines
Dengue Vaccines
mutants
serotypes
viruses
Arboviruses
Attenuated Vaccines
arboviruses
Dengue
Macaca fascicularis
Macaca
indigenous species
methylcobalamin-coenzyme M methyltransferase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Züst, R., Li, S. H., Xie, X., Velumani, S., Chng, M., Toh, Y. X., ... Fink, K. (2018). Characterization of a candidate tetravalent vaccine based on 2’-O-methyltransferase mutants. PLoS One, 13(1), [e0189262]. https://doi.org/10.1371/journal.pone.0189262

Characterization of a candidate tetravalent vaccine based on 2’-O-methyltransferase mutants. / Züst, Roland; Li, Shi Hua; Xie, Xuping; Velumani, Sumathy; Chng, Melissa; Toh, Ying Xiu; Zou, Jing; Dong, Hongping; Shan, Chao; Pang, Jassia; Qin, Cheng Feng; Newell, Evan W.; Shi, Pei-Yong; Fink, Katja.

In: PLoS One, Vol. 13, No. 1, e0189262, 01.01.2018.

Research output: Contribution to journalArticle

Züst, R, Li, SH, Xie, X, Velumani, S, Chng, M, Toh, YX, Zou, J, Dong, H, Shan, C, Pang, J, Qin, CF, Newell, EW, Shi, P-Y & Fink, K 2018, 'Characterization of a candidate tetravalent vaccine based on 2’-O-methyltransferase mutants', PLoS One, vol. 13, no. 1, e0189262. https://doi.org/10.1371/journal.pone.0189262
Züst, Roland ; Li, Shi Hua ; Xie, Xuping ; Velumani, Sumathy ; Chng, Melissa ; Toh, Ying Xiu ; Zou, Jing ; Dong, Hongping ; Shan, Chao ; Pang, Jassia ; Qin, Cheng Feng ; Newell, Evan W. ; Shi, Pei-Yong ; Fink, Katja. / Characterization of a candidate tetravalent vaccine based on 2’-O-methyltransferase mutants. In: PLoS One. 2018 ; Vol. 13, No. 1.
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