title: Molecular and immunological characterization of a DNA-launched yellow fever virus 17D infectious clone.
abstract: Yellow fever virus (YFV)-17D is an empirically developed, highly effective live-attenuated vaccine that has been administered to human beings for almost a century. YFV-17D has stood as a paradigm for a successful viral vaccine, and has been exploited as a potential virus vector for the development of recombinant vaccines against other diseases. In this study, a DNA-launched YFV-17D construct (pBeloBAC-FLYF) was explored as a new modality to the standard vaccine to combine the commendable features of both DNA vaccine and live-attenuated viral vaccine. The DNA-launched YFV-17D construct was characterized extensively both in cell culture and in mice. High titres of YFV-17D were generated upon transfection of the DNA into cells, whereas a mutant with deletion in the capsid-coding region (pBeloBAC-YF/ΔC) was restricted to a single round of infection, with no release of progeny virus. Homologous prime-boost immunization of AAD mice with both pBeloBAC-FLYF and pBeloBAC-YF/ΔC elicited specific dose-dependent cellular immune response against YFV-17D. Vaccination of A129 mice with pBeloBAC-FLYF resulted in the induction of YFV-specific neutralizing antibodies in all vaccinated subjects. These promising results underlined the potential of the DNA-launched YFV both as an alternative to standard YFV-17D vaccination and as a vaccine platform for the development of DNA-based recombinant YFV vaccines.
authors.affiliation: Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, P. O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, P. O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Dalebout
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, NIH Regional Bio-containment Laboratory, University of Louisville, KY, USA.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
authors.affiliation: Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, P. O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bredenbeek
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: David
authors.initials: D
authors.lastname: Franco
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000235:genetics* / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology; D015004:Yellow Fever / Q000276:immunology* / Q000821:virology*; D022341:Yellow Fever Vaccine / Q000235:genetics* / Q000276:immunology*; D015005:Yellow fever virus / Q000235:genetics* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014765:Viral Vaccines; D022341:Yellow Fever Vaccine; D004247:DNA