title: Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice.
abstract: 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.
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Tretyakova
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Nickols
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA.
authors.forename: Rachmat
authors.initials: R
authors.lastname: Hidajat
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Jokinen
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
authors.affiliation: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA. Electronic address: ppushko@medigen-usa.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Pushko
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines; D014779:Virus Replication; D015004:Yellow Fever / Q000276:immunology* / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014765:Viral Vaccines; D022341:Yellow Fever Vaccine
keywords: 17D vaccine; DNA vaccine; Flavivirus; Live attenuated vaccine; YFV; Yellow fever virus