DNA vaccination protects mice against Zika virus-induced damage to the testes.
Bryan D GriffinKar MuthumaniBryce M WarnerAnna MajerMable HaganJonathan AudetDerek R SteinCharlene RanadheeraTrina RacineMarc-Antoine De La VegaJocelyne PiretStephanie KucasKaylie N TranKathy L FrostChristine De GraffGeoff SouleLeanne ScharikowJennifer ScottGordon McTavishValerie SmidYoung K ParkJoel N MaslowNiranjan Y SardesaiJ Joseph KimXiao-Jian YaoAlexander BelloRobbin LindsayGuy BoivinStephanie A BoothDarwyn KobasaCarissa Embury-HyattDavid SafronetzDavid B WeinerGary P KobingerPublished in: Nature communications (2017)
Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.
Keyphrases
- zika virus
- dengue virus
- aedes aegypti
- clinical trial
- circulating tumor
- oxidative stress
- single molecule
- endothelial cells
- type diabetes
- dendritic cells
- randomized controlled trial
- stem cells
- sars cov
- risk assessment
- mental health
- high glucose
- high fat diet induced
- machine learning
- early onset
- climate change
- electronic health record
- drug induced
- skeletal muscle
- mouse model
- mesenchymal stem cells
- insulin resistance
- metabolic syndrome
- human health
- bone marrow
- phase ii