关键词: Baculovirus vector Bioreactor Immunity Silkworm Virus-like particles

Mesh : Animals Bombyx / immunology Mice COVID-19 Vaccines / immunology Mice, Inbred BALB C Vaccines, Virus-Like Particle / immunology genetics SARS-CoV-2 / immunology genetics Antibodies, Viral / immunology blood COVID-19 / prevention & control immunology Female Cell Line Baculoviridae / genetics immunology Capsid Proteins / immunology genetics Cytokines / metabolism Vaccines, Synthetic / immunology genetics

来  源:   DOI:10.1016/j.ijbiomac.2024.134027

Abstract:
COVID-19, caused by the novel coronavirus SARS-CoV-2, has presented a significant challenge to global health, security, and the economy. Vaccination is considered a crucial measure in preventing virus transmission. The silkworm bioreactor has gained widespread usage in antigen presentation, monoclonal antibody preparation, and subunit vaccine development due to its safety, efficiency, convenience, and cost-effectiveness. In this study, we employed silkworm BmN cells and the silkworm MultiBac multigene co-expression system to successfully produce two prototype vaccines: a recombinant baculovirus vector vaccine (NPV) co-displaying the SARS-CoV-2 virus capsid protein and a capsid protein virus-like particle (VLP) vaccine. Following the purification of these vaccines, we immunized BALB/c mice to evaluate their immunogenicity. Our results demonstrated that both VLP and NPV prototype vaccines effectively elicited robust immune responses in mice. However, when equal inoculation doses between groups were compared, the recombinant NPV vaccine exhibited significantly higher serum antibody titers and increased expression of spleen cytokines and lymphocyte immune regulatory factors compared to the VLP group. These results suggested an increased immune efficacy of the recombinant NPV vaccine. Conversely, the VLP prototype vaccine displayed more pronounced effects on lymphocyte cell differentiation induction. This study successfully constructed two distinct morphological recombinant vaccine models and systematically elucidated their differences in humoral immune response and lymphocyte differentiation rate. Furthermore, it has fully harnessed the immense potential of silkworm bioreactors for vaccine research and development, providing valuable technical insights for studying mutated viruses like coronaviruses.
摘要:
由新型冠状病毒SARS-CoV-2引起的COVID-19对全球健康构成了重大挑战,安全,和经济。疫苗接种被认为是预防病毒传播的关键措施。家蚕生物反应器在抗原呈递中得到了广泛的应用,单克隆抗体制备,和亚单位疫苗的开发,由于其安全性,效率,便利性,和成本效益。在这项研究中,我们利用家蚕BmN细胞和家蚕MultiBac多基因共表达系统成功生产了两种原型疫苗:共展示SARS-CoV-2病毒衣壳蛋白的重组杆状病毒载体疫苗(NPV)和衣壳蛋白病毒样颗粒(VLP)疫苗。这些疫苗纯化后,我们免疫BALB/c小鼠以评估其免疫原性。我们的结果表明,VLP和NPV原型疫苗均有效地在小鼠中引起强烈的免疫应答。然而,当两组之间的接种剂量相等时,与VLP组相比,重组NPV疫苗表现出显著更高的血清抗体滴度和脾细胞因子和淋巴细胞免疫调节因子表达增加.这些结果表明重组NPV疫苗的免疫效力增加。相反,VLP原型疫苗对淋巴细胞分化诱导显示出更明显的效果。本研究成功构建了两种不同的形态学重组疫苗模型,并系统阐明了它们在体液免疫应答和淋巴细胞分化率方面的差异。此外,它充分利用了家蚕生物反应器用于疫苗研发的巨大潜力,为研究突变病毒如冠状病毒提供有价值的技术见解。
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