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 language | English (US) |
|---|---|
| Pages (from-to) | 13694-13705 |
| Number of pages | 12 |
| Journal | Journal of Virology |
| Volume | 87 |
| Issue number | 24 |
| DOIs | |
| State | Published - Dec 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Virology
Cite this
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. / Li, Xiao Feng; Deng, Yong Qiang; Yang, Hui Qiang; Zhao, Hui; Jiang, Tao; Yu, Xue Dong; Li, Shi Hua; Ye, Qing; Zhu, Shun Ya; Wang, Hong Jiang; Zhang, Yu; Ma, Jie; Yu, Yong Xin; Liu, Zhong Yu; Li, Yu Hua; Qin, E. De; Shi, Pei-Yong; Qin, Cheng Feng.
In: Journal of Virology, Vol. 87, No. 24, 12.2013, p. 13694-13705.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Li, Xiao Feng
AU - Deng, Yong Qiang
AU - Yang, Hui Qiang
AU - Zhao, Hui
AU - Jiang, Tao
AU - Yu, Xue Dong
AU - Li, Shi Hua
AU - Ye, Qing
AU - Zhu, Shun Ya
AU - Wang, Hong Jiang
AU - Zhang, Yu
AU - Ma, Jie
AU - Yu, Yong Xin
AU - Liu, Zhong Yu
AU - Li, Yu Hua
AU - Qin, E. De
AU - Shi, Pei-Yong
AU - Qin, Cheng Feng
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84888030037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888030037&partnerID=8YFLogxK
U2 - 10.1128/JVI.00931-13
DO - 10.1128/JVI.00931-13
M3 - Article
C2 - 24109223
AN - SCOPUS:84888030037
VL - 87
SP - 13694
EP - 13705
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 24
ER -