Highly efficient production of a dengue pseudoinfectious virus

Xiaowu Pang, Yinhan Guo, Yanfei Zhou, Wenchuan Fu, Xinbin Gu

Research output: Contribution to journalArticle

Abstract

Dengue is a major infectious disease that affects people living in tropical and subtropical regions around the world. The causative agents are dengue virus serotype 1, 2, 3, and 4 (DENV1, 2, 3, and 4). Developing a vaccine for dengue is a high priority for public health, but traditional methods have faced numerous obstacles due to the unique immunopathogenesis of dengue virus infection. Here, we report a novel dengue vaccine candidate based on dengue pseudoinfectious virus (PIV) produced by the incorporation of a dengue subgenomic replicon into viral particles in highly efficient packaging cells. The subgenomic replicon was constructed by deleting the capsid protein (C) gene from the dengue viral genome and optimizing the signal peptide sequence of pre-membrane protein (prM) to facilitate the formation of viral particles. Packaging cells were developed for inducible expression of a bi-protein Cpr, where the protein pr is the "pr" segment of viral protein prM that holds the protein C on the endoplasmic reticulum (ER). When the replicon was introduced into the packaging cells, protein C was released from the bi-protein Cpr by a replicon-encoded viral protease. Coordinate expression of viral structural proteins by the replicon and packaging cells led to the incorporation of the replicon into viral particle to produce PIVs. Animal tests showed that the dengue PIV vaccine was highly immunogenic and the immune response protected mice challenged with a hundred-fold LD50 inoculation of dengue virus. The method described here has the potential to be applied to vaccine development for other flaviviruses.

Original languageEnglish (US)
Pages (from-to)3854-3860
Number of pages7
JournalVaccine
Volume32
Issue number30
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

replicon
Dengue virus
Replicon
Dengue Virus
dengue
Product Packaging
packaging
Dengue
Dengue Vaccines
Protein C
virion
Virion
viral proteins
vaccines
proteins
membrane proteins
Membrane Proteins
Vaccines
cells
Flaviviridae

Keywords

  • Dengue vaccine
  • Immunogenicity
  • Packaging cell
  • Pseudoinfectious virus
  • Replicon

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Pang, X., Guo, Y., Zhou, Y., Fu, W., & Gu, X. (2014). Highly efficient production of a dengue pseudoinfectious virus. Vaccine, 32(30), 3854-3860. https://doi.org/10.1016/j.vaccine.2014.03.091

Highly efficient production of a dengue pseudoinfectious virus. / Pang, Xiaowu; Guo, Yinhan; Zhou, Yanfei; Fu, Wenchuan; Gu, Xinbin.

In: Vaccine, Vol. 32, No. 30, 2014, p. 3854-3860.

Research output: Contribution to journalArticle

Pang, X, Guo, Y, Zhou, Y, Fu, W & Gu, X 2014, 'Highly efficient production of a dengue pseudoinfectious virus', Vaccine, vol. 32, no. 30, pp. 3854-3860. https://doi.org/10.1016/j.vaccine.2014.03.091
Pang, Xiaowu ; Guo, Yinhan ; Zhou, Yanfei ; Fu, Wenchuan ; Gu, Xinbin. / Highly efficient production of a dengue pseudoinfectious virus. In: Vaccine. 2014 ; Vol. 32, No. 30. pp. 3854-3860.
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