Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus.
Whitney R BaldwinHolli A GieblerJanae L StovallGinger YoungKelly J BohningHansi J DeanJill A LivengoodClaire Y-H HuangPublished in: Nature communications (2021)
The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development.
Keyphrases
- zika virus
- dengue virus
- aedes aegypti
- endothelial cells
- escherichia coli
- pseudomonas aeruginosa
- high fat diet induced
- immune response
- dna methylation
- metabolic syndrome
- adipose tissue
- stem cells
- mesenchymal stem cells
- genome wide
- copy number
- cell cycle arrest
- pi k akt
- electronic health record
- big data
- candida albicans
- nk cells
- artificial intelligence
- pluripotent stem cells