Biotechnology and Biopharmaceuticals Laboratory, Pathophysiology Department, School of Biological Sciences, Universidad de Concepción, Víctor Lamas 1290, Concepción P.O. Box 160C, Chile.
Department of Medicine, Division of Gastroenterology, Miller School of Medicine, University of Miami, Miami, FL 33146, USA.
Int J Mol Sci. 2024 Aug 10;25(16):8734. doi: 10.3390/ijms25168734.
Multivalent live-attenuated or inactivated vaccines are often used to control the bovine viral diarrhea disease (BVD). Still, they retain inherent disadvantages and do not provide the expected protection. This study developed a new vaccine prototype, including the external segment of the E2 viral protein from five different subgenotypes selected after a massive screening. The E2 proteins of every subgenotype (1aE2, 1bE2, 1cE2, 1dE2, and 1eE2) were produced in mammalian cells and purified by IMAC. An equimolar mixture of E2 proteins formulated in an oil-in-water adjuvant made up the vaccine candidate, inducing a high humoral response at 50, 100, and 150 µg doses in sheep. A similar immune response was observed in bovines at 50 µg. The cellular response showed a significant increase in the transcript levels of relevant Th1 cytokines, while those corresponding to the Th2 cytokine IL-4 and the negative control were similar. High levels of neutralizing antibodies against the subgenotype BVDV1a demonstrated the effectiveness of our vaccine candidate, similar to that observed in the sera of animals vaccinated with the commercial vaccine. These results suggest that our vaccine prototype could become an effective recombinant vaccine against the BVD.
多价活疫苗或灭活疫苗常用于控制牛病毒性腹泻病（BVD）。然而，它们仍存在固有缺陷，不能提供预期的保护。本研究开发了一种新的疫苗原型，包括经过大规模筛选后选择的五个不同亚基因组的 E2 病毒蛋白的外部片段。每个亚基因组（1aE2、1bE2、1cE2、1dE2 和 1eE2）的 E2 蛋白都在哺乳动物细胞中产生，并通过 IMAC 纯化。E2 蛋白的等摩尔混合物在水包油佐剂中配制，在 50、100 和 150µg 剂量下在绵羊中诱导高体液反应。在 50µg 时，在牛中观察到类似的免疫反应。细胞反应显示相关 Th1 细胞因子的转录水平显著增加，而 Th2 细胞因子 IL-4 和阴性对照的转录水平则相似。针对 BVDV1a 亚基因组的中和抗体水平较高，表明我们的疫苗候选物有效，类似于用商业疫苗接种的动物血清中观察到的效果。这些结果表明，我们的疫苗原型可能成为针对 BVD 的有效重组疫苗。
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