A chimeric dengue virus vaccine using japanese encephalitis virus vaccine strain SA14-14-2 as backbone is immunogenic and protective against either parental virus in mice and nonhuman primates

Xiao Feng Li, Yong Qiang Deng, Hui Qiang Yang, Hui Zhao, Tao Jiang, Xue Dong Yu, Shi Hua Li, Qing Ye, Shun Ya Zhu, Hong Jiang Wang, Yu Zhang, Jie Ma, Yong Xin Yu, Zhong Yu Liu, Yu Hua Li, E. De Qin, Pei-Yong Shi, Cheng Feng Qin

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40 Scopus citations

Abstract

The development of a safe and efficient dengue vaccine represents a global challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated flavivirus have been well developed as vaccine candidates by using reverse genetics. In this study, based on the full-length infectious cDNA clone of the well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed and constructed by replacement with the premembrane and envelope genes of dengue 2 virus. The recovered chimeric virus showed growth and plaque properties similar to those of the parental DENV in mammalian and mosquito cells. ChinDENV was highly attenuated in mice, and no viremia was induced in rhesus monkeys upon subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation phenotype after serial 15 passages in cultured cells. A single immunization with various doses of ChinDENV elicited strong neutralizing antibodies in a dose-dependent manner. When vaccinated monkeys were challenged with wild-type DENV, all animals except one that received the lower dose were protected against the development of viremia. Furthermore, immunization with Chin- DENV conferred efficient cross protection against lethal JEV challenge in mice in association with robust cellular immunity induced by the replicating nonstructural proteins. Taken together, the results of this preclinical study well demonstrate the great potential of ChinDENV for further development as a dengue vaccine candidate, and this kind of chimeric flavivirus based on JE vaccine virus represents a powerful tool to deliver foreign antigens.

Original languageEnglish (US)
Pages (from-to)13694-13705
Number of pages12
JournalJournal of Virology
Volume87
Issue number24
DOIs
StatePublished - Dec 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Li, X. F., Deng, Y. Q., Yang, H. Q., Zhao, H., Jiang, T., Yu, X. D., Li, S. H., Ye, Q., Zhu, S. Y., Wang, H. J., Zhang, Y., Ma, J., Yu, Y. X., Liu, Z. Y., Li, Y. H., Qin, E. D., Shi, P-Y., & Qin, C. F. (2013). A chimeric dengue virus vaccine using japanese encephalitis virus vaccine strain SA14-14-2 as backbone is immunogenic and protective against either parental virus in mice and nonhuman primates. Journal of Virology, 87(24), 13694-13705. https://doi.org/10.1128/JVI.00931-13