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在小鼠中对由G蛋白和M蛋白组成的基于呼吸道合胞病毒前融合F蛋白的病毒样颗粒进行免疫原性评估。

Immunogenicity evaluation of respiratory syncytial virus prefusogenic-F based virus-like-particles consisting of G and M proteins in mice.

作者信息

Mandviwala Ahmedali S, Munje Archana Kulkarni, Huckriede Anke L W, Arankalle Vidya A, Patil Harshad P

机构信息

Department of Communicable Diseases, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India.

Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

出版信息

Vaccine. 2025 May 22;56:127203. doi: 10.1016/j.vaccine.2025.127203. Epub 2025 May 6.

Abstract

Human respiratory syncytial virus (hRSV) is a major cause of severe respiratory disease in infants and young children worldwide. Studies have shown that fusion-inactive prefusogenic fusion protein (F), a partially cleaved F protein made by inserting mutations in the furin cleavage site II of the fusion protein sequence, is equally immunogenic as the prefusion F and provides higher protection than postfusion structures of the F protein. Here we have developed respiratory syncytial virus (RSV) virus-like-particles (RSV-VLPs) containing baculovirus-produced prefusogenic-F, RSV glycoprotein and matrix proteins and studied their protective efficacy in BALB/c mice. Morphology and successful assembly of VLPs were confirmed by electron microscopy and western blot. Mice immunized with the VLPs developed higher levels of serum IgG and neutralizing antibodies as compared to mice immunized with inactivated RSV. The VLPs induced higher levels of IFN-γ and IL-4, enhanced T cell responses and prevented lung pathology after RSV challenge. Overall, our results indicate that RSV-VLPs containing prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

摘要

人呼吸道合胞病毒(hRSV)是全球婴幼儿严重呼吸道疾病的主要病因。研究表明,融合无活性的前融合融合蛋白(F)是通过在融合蛋白序列的弗林蛋白酶切割位点II中插入突变而产生的部分切割F蛋白,其免疫原性与前融合F相同,并且比F蛋白的后融合结构提供更高的保护作用。在此,我们开发了含有杆状病毒产生的前融合-F、RSV糖蛋白和基质蛋白的呼吸道合胞病毒(RSV)病毒样颗粒(RSV-VLPs),并研究了它们在BALB/c小鼠中的保护效果。通过电子显微镜和蛋白质印迹法确认了VLPs的形态和成功组装。与用灭活RSV免疫的小鼠相比,用VLPs免疫的小鼠产生了更高水平的血清IgG和中和抗体。VLPs诱导了更高水平的IFN-γ和IL-4,增强了T细胞反应,并在RSV攻击后预防了肺部病变。总体而言,我们的结果表明,含有前融合F、糖蛋白和基质蛋白的RSV-VLPs是一种潜在的抗RSV疫苗候选物。

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