Jiang Xiaohong, Dalebout Tim J, Lukashevich Igor S, Bredenbeek Peter J, Franco David
Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, P. O. Box 9600, 2300 RC Leiden, The Netherlands.
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.
J Gen Virol. 2015 Apr;96(Pt 4):804-814. doi: 10.1099/jgv.0.000026. Epub 2014 Dec 16.
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.
黄热病病毒（YFV）-17D是一种凭经验研发的高效减毒活疫苗，已用于人类接种近一个世纪。YFV-17D一直是成功病毒疫苗的典范，并已被用作开发针对其他疾病的重组疫苗的潜在病毒载体。在本研究中，探索了一种DNA启动的YFV-17D构建体（pBeloBAC-FLYF），作为标准疫苗的一种新形式，以结合DNA疫苗和减毒活病毒疫苗的优良特性。对DNA启动的YFV-17D构建体在细胞培养和小鼠中进行了广泛表征。将DNA转染到细胞中后可产生高滴度的YFV-17D，而衣壳编码区缺失的突变体（pBeloBAC-YF/ΔC）仅限于单轮感染，无子代病毒释放。用pBeloBAC-FLYF和pBeloBAC-YF/ΔC对AAD小鼠进行同源初免-加强免疫，引发了针对YFV-17D的特异性剂量依赖性细胞免疫反应。用pBeloBAC-FLYF对A129小鼠进行疫苗接种，在所有接种的小鼠体内均诱导出YFV特异性中和抗体。这些有前景的结果突显了DNA启动的YFV作为标准YFV-17D疫苗接种替代方法以及作为基于DNA的重组YFV疫苗开发的疫苗平台的潜力。
