Molecular and immunological characterization of a DNA-launched yellow fever virus 17D infectious clone

• Published in: Journal of general virology Vol. 96; no. 4; pp. 804 - 814
• Main Authors: Jiang, Xiaohong, Dalebout, Tim J., Lukashevich, Igor S., Bredenbeek, Peter J., Franco, David
• Format: Journal Article
• Language: English
• Published: England Society for General Microbiology 01.04.2015
• Subjects: Animal; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Cell Line; Cricetinae; DNA - genetics; DNA - immunology; Female; Genetic Vectors - genetics; Genetic Vectors - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic - genetics; Mice, Transgenic - immunology; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Viral Vaccines - genetics; Viral Vaccines - immunology; Virus Replication - genetics; Virus Replication - immunology; Yellow Fever - immunology; Yellow Fever - virology; Yellow Fever Vaccine - genetics; Yellow Fever Vaccine - immunology; Yellow fever virus - genetics; Yellow fever virus - immunology
• ISSN: 0022-1317; 1465-2099; 1465-2099
• DOI: 10.1099/jgv.0.000026

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.