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dc.contributor.authorPoonsook Keelapangen_US
dc.contributor.authorNarong Nitatpattanaen_US
dc.contributor.authorAmporn Suphatrakulen_US
dc.contributor.authorSurat Punyahathaikulen_US
dc.contributor.authorRungtawan Sriburien_US
dc.contributor.authorRojjanaporn Pulmanausahakulen_US
dc.contributor.authorSathit Pichyangkulen_US
dc.contributor.authorPrida Malasiten_US
dc.contributor.authorSutee Yoksanen_US
dc.contributor.authorNopporn Sittisombuten_US
dc.description.abstractIn the absence of a vaccine or sustainable vector control measures, illnesses caused by dengue virus infection remain an important public health problem in many tropical countries. During the export of dengue virus particles, furin-mediated cleavage of the prM envelope protein is usually incomplete, thus generating a mixture of immature, partially mature and mature extracellular particles. Variations in the arrangement and conformation of the envelope proteins among these particles may be associated with their different roles in shaping the antibody response. In an attempt to improve upon live, attenuated dengue vaccine approaches, a mutant chimeric virus, with enhanced prM cleavage, was generated by introducing a cleavage-enhancing substitution into a chimeric DENV-1/2 virus genome, encoding the prM. +. E sequence of a recent DENV-1 isolate under an attenuated DENV-2 genetic background. A modest increase in virus specific infectivity observed in the mutant chimeric virus affected neither the attenuation phenotype, when assessed in the suckling mouse neurovirulence model, nor multiplication in mosquitoes. The two chimeric viruses induced similar levels of anti-DENV-1 neutralizing antibody response in mice and rhesus macaques, but more efficient control of viremia during viral challenge was observed in macaques immunized with the mutant chimeric virus. These results indicate that the DENV-1/2 chimeric virus, with enhanced prM cleavage, could be useful as an alternative live, attenuated vaccine candidate for further tests in humans. © 2013 Elsevier Ltd.en_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleGeneration and preclinical evaluation of a DENV-1/2 prM+E chimeric live attenuated vaccine candidate with enhanced prM cleavageen_US
article.volume31en_US Mai Universityen_US Universityen_US National Center for Genetic Engineering and Biotechnologyen_US Forces Research Institute of Medical Sciences, Thailanden_US
Appears in Collections:CMUL: Journal Articles

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