Harrison Jessica J, Nguyen Wilson, Morgan Mahali S, Tang Bing, Habarugira Gervais, de Malmanche Henry, Freney Morgan E, Modhiran Naphak, Watterson Daniel, Cox Abigail L, Yan Kexin, Yuen Nicholas K Y, Bowman Dylan H, Kirkland Peter D, Bielefeldt-Ohmann Helle, Suhrbier Andreas, Hall Roy A, Rawle Daniel J, Hobson-Peters Jody
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, 4072, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, 4029, Australia.
NPJ Vaccines. 2024 Jul 31;9(1):134. doi: 10.1038/s41541-024-00903-2.
In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus (JEV) caused an unprecedented and widespread outbreak of disease in pigs and humans in Australia. As no veterinary vaccines against JEV are approved in Australia and all current approved human and veterinary vaccines are derived from genotype (G) III JEV strains, we used the recently described insect-specific Binjari virus (BinJV) chimeric flavivirus vaccine technology to produce a JEV GIV vaccine candidate. Herein we describe the production of a chimeric virus displaying the structural prM and E proteins of a JEV GIV isolate obtained from a stillborn piglet (JEV) in the genomic backbone of BinJV (BinJ/JEVprME). BinJ/JEVprME was shown to be antigenically indistinguishable from the JEV parental virus by K analysis and a panel of JEV-reactive monoclonal antibodies in ELISA. BinJ/JEVprME replicated efficiently in C6/36 cells, reaching titres of >10 infectious units/mL - an important attribute for vaccine manufacture. As expected, BinJ/JEVprME failed to replicate in a variety of vertebrate cells lines. When used to immunise mice, the vaccine induced a potent virus neutralising response against JEV and to GII and GIII JEV strains. The BinJ/JEVprME vaccine provided complete protection against lethal challenge with JEV, whilst also providing partial protection against viraemia and disease for the related Murray Valley encephalitis virus. Our results demonstrate that BinJ/JEVprME is a promising vaccine candidate against JEV.
2022年，一株日本脑炎病毒（JEV）基因型IV（GIV）毒株在澳大利亚引发了猪和人类中前所未有的广泛疾病暴发。由于澳大利亚没有批准用于预防JEV的兽用疫苗，且目前所有批准的人用和兽用疫苗均源自基因型（G）III JEV毒株，我们利用最近描述的昆虫特异性宾贾里病毒（BinJV）嵌合黄病毒疫苗技术制备了一种JEV GIV候选疫苗。在此，我们描述了一种嵌合病毒的制备，该病毒在BinJV的基因组骨架中展示了从一头死产仔猪分离得到的JEV GIV毒株的结构蛋白prM和E（BinJ/JEVprME）。通过K分析和ELISA中的一组JEV反应性单克隆抗体，证明BinJ/JEVprME在抗原性上与JEV亲本病毒无法区分。BinJ/JEVprME在C6/36细胞中高效复制，滴度>10个感染单位/mL，这是疫苗生产的一个重要特性。正如预期的那样，BinJ/JEVprME在多种脊椎动物细胞系中无法复制。当用于免疫小鼠时，该疫苗诱导了针对JEV以及GII和GIII JEV毒株的强效病毒中和反应。BinJ/JEVprME疫苗提供了针对JEV致死性攻击的完全保护，同时也为相关的墨累谷脑炎病毒提供了针对病毒血症和疾病的部分保护。我们的结果表明，BinJ/JEVprME是一种有前景的抗JEV候选疫苗。
