Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

•The iDNA® platform combines advantages of DNA and live attenuated vaccines.•Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo.•Safety of iDNA-generated 17D virus was confirmed in AG129 mice.•BALB/c mice seroconverted after a single-dose vaccination with iDNA.•YF virus-neutralizing response was elicited in iDNA-vaccinated mice.

Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF.