Abstract
The mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation: small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.
Highlights
Zika virus (ZIKV) is an emerging mosquito-borne pathogen from the genus Flavivirus[1,2,3], which contains other arthropod-borne pathogens such as yellow fever virus (YFV), dengue virus type 1 to 4 (DENV1 to DENV4), and Japanese encephalitis virus (JEV)[4]
We constructed the infectious clone of our chimeric dengue/Zika virus, VacDZ, (Fig. 1), by modifying our existing DENV2-16681 infectious clone[35]
We developed a chimeric dengue/Zika virus called VacDZ as a vaccine candidate against ZIKV
Summary
Zika virus (ZIKV) is an emerging mosquito-borne pathogen from the genus Flavivirus[1,2,3], which contains other arthropod-borne pathogens such as yellow fever virus (YFV), dengue virus type 1 to 4 (DENV1 to DENV4), and Japanese encephalitis virus (JEV)[4]. ZIKV is typically spread by the Aedes aegypti and Aedes albopictus mosquitoes, past outbreaks have been linked to the Aedes hensilli mosquito[5,6]. ZIKV recently emerged to cause a larger outbreak in the Americas[1,2,3]. May 2017, ZIKV is estimated to have caused an estimated 8.5 million symptomatic infections in Brazil alone[3]. ZIKV infection is reported to be asymptomatic in a majority of patients, with the reported asymptomatic rate varying from 29% to 82%, and with 80% being the commonly cited figure[7]. Symptomatic ZIKV infection typically presents as an acute and self-limiting febrile disease, with symptoms such as maculopapular rash, joint pain, and conjunctivitis[1,2].
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