AI Article Synopsis
- Dengue virus (DENV) is widespread and affects around 400 million people annually, with 96 million cases leading to severe illness in about 500,000 of those.
- The only existing vaccine has limited efficacy and is only suitable for areas with high dengue rates.
- Researchers developed a new tetravalent, live-attenuated dengue vaccine using 2'-O-methyltransferase mutants from all four DENV serotypes, which showed promising results in mice and macaques by being both safe and effective at eliciting immunity.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751980 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189262 | PLOS |
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