Chineka Nicole, Whittle Leah, Douglass Nicola, Williamson Anna-Lise, Chapman Ros
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Hum Vaccin Immunother. 2025 Dec;21(1):2480891. doi: 10.1080/21645515.2025.2480891. Epub 2025 Apr 11.
Bovine coronavirus (BCoV) causes significant pneumo-enteric infections in cattle and other ruminants. A BCoV-like coronavirus was previously found in a symptomatic human child and shares 97.1% sequence identity with one of the more prevalent human coronaviruses, HCoV-OC43. Zoonosis of a virulent BCoV from livestock is a feasible threat. Lumpy skin disease virus (LSDV) is a poxvirus that can be used as a live attenuated dual vaccine vector in cattle and potentially as a replication-deficient vaccine vector, in humans. This paper explores the development of a vaccine, considering the increasingly significant One Health approach, which recognizes the importance of curbing disease at the animal-human interface to prevent future epizootics and pandemics. A recombinant LSDV (LSDV-BCoV-K1L) was developed to express the spike and nucleocapsid proteins of BCoV. The spike and nucleocapsid antigens used in this vaccine were derived from consensus sequences of 38 spike and 24 nucleocapsid amino acid sequences, encompassing multiple BCoV genotypes. The insertion of the foreign gene cassette between LSDV open reading frames 49 and 50 was verified using polymerase chain reaction and DNA sequencing. Furthermore, western blot analysis confirmed the expression of BCoV spike and nucleocapsid proteins in cells infected with LSDV-BCoV-K1L. The immunogenicity of LSDV-BCoV-K1L was evaluated in mice and compared to the parent virus, nLSDVSODis-UCT. Mice immunized with LSDV-BCoV-K1L produced nucleocapsid-specific T-cells and high levels of spike-specific antibodies. This combined vaccine targeting both lumpy skin disease virus and BCoV requires further evaluation.
牛冠状病毒（BCoV）可在牛和其他反刍动物中引发严重的肺肠感染。此前在一名有症状的人类儿童中发现了一种类似BCoV的冠状病毒，它与一种较为常见的人类冠状病毒HCoV-OC43的序列同一性为97.1%。来自家畜的强毒株BCoV引发人畜共患病是一种切实可行的威胁。结节性皮肤病病毒（LSDV）是一种痘病毒，可作为牛的减毒活双疫苗载体，在人类中可能用作复制缺陷型疫苗载体。本文考虑到日益重要的“同一健康”方法，探讨了一种疫苗的研发，该方法认识到在动物与人类的界面控制疾病对于预防未来的动物流行病和大流行的重要性。研发了一种重组LSDV（LSDV-BCoV-K1L）来表达BCoV的刺突蛋白和核衣壳蛋白。该疫苗中使用的刺突蛋白和核衣壳抗原源自38个刺突氨基酸序列和24个核衣壳氨基酸序列的共有序列，涵盖了多种BCoV基因型。利用聚合酶链反应和DNA测序验证了外源基因盒插入LSDV开放阅读框49和50之间。此外，蛋白质印迹分析证实了在感染LSDV-BCoV-K1L的细胞中表达了BCoV刺突蛋白和核衣壳蛋白。在小鼠中评估了LSDV-BCoV-K1L的免疫原性，并与亲本病毒nLSDVSODis-UCT进行了比较。用LSDV-BCoV-K1L免疫的小鼠产生了核衣壳特异性T细胞和高水平的刺突特异性抗体。这种针对结节性皮肤病病毒和BCoV的联合疫苗需要进一步评估。
