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表达呼吸道合胞病毒预融合蛋白和G蛋白的病毒样颗粒疫苗可提供针对呼吸道合胞病毒攻击感染的保护。

Virus-like Particle Vaccine Expressing the Respiratory Syncytial Virus Pre-Fusion and G Proteins Confers Protection against RSV Challenge Infection.

作者信息

Lee Su-Hwa, Chu Ki-Back, Kim Min-Ju, Mao Jie, Eom Gi-Deok, Yoon Keon-Woong, Ahmed Md Atique, Quan Fu-Shi

机构信息

Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea.

Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea.

出版信息

Pharmaceutics. 2023 Feb 27;15(3):782. doi: 10.3390/pharmaceutics15030782.

Abstract

Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in children and the elderly. However, there are no effective antiviral drugs or licensed vaccines available for RSV infection. Here, RSV virus-like particle (VLP) vaccines expressing Pre-F, G, or Pre-F and G proteins on the surface of influenza virus matrix protein 1 (M1) were produced using the baculovirus expression system, and their protective efficacy was evaluated in mice. The morphology and successful assembly of VLPs were confirmed by transmission electron microscope (TEM) and Western blot. High levels of serum IgG antibody response were detected in VLP-immunized mice, and significantly higher levels of IgG2a and IgG2b were found in the Pre-F+G VLP immunization group compared to the unimmunized control. Serum-neutralizing activity was higher in the VLP immunization groups compared to the naïve group, with Pre-F+G VLPs demonstrating superior neutralizing activity to the single antigen-expressing VLP groups. Pulmonary IgA and IgG responses were generally comparable across the immunization groups, with VLPs expressing the Pre-F antigen eliciting higher IFN-γ in spleens. The frequencies of eosinophils and IL-4-producing CD4 T cell populations were substantially lower in the lungs of VLP-immunized mice, with the PreF+G vaccine inducing a significant increase in CD4 and CD8 T cells. VLP immunization significantly decreased the viral titer and inflammation in the lungs of mice, with Pre-F+G VLPs conferring the best protection. In conclusion, our present study suggests that the Pre-F+G VLPs could be a potential vaccine candidate against RSV infection.

摘要

呼吸道合胞病毒(RSV)可导致儿童和老年人发生严重的下呼吸道疾病。然而,目前尚无针对RSV感染的有效抗病毒药物或获批疫苗。在此,我们利用杆状病毒表达系统制备了在流感病毒基质蛋白1(M1)表面表达前体融合蛋白(Pre-F)、糖蛋白(G)或Pre-F和G蛋白的RSV病毒样颗粒(VLP)疫苗,并在小鼠中评估了它们的保护效力。通过透射电子显微镜(TEM)和蛋白质免疫印迹法证实了VLP的形态和成功组装。在VLP免疫的小鼠中检测到高水平的血清IgG抗体反应,与未免疫对照组相比,Pre-F+G VLP免疫组中IgG2a和IgG2b的水平显著更高。与未免疫组相比,VLP免疫组的血清中和活性更高,Pre-F+G VLP表现出比单一抗原表达VLP组更强的中和活性。各免疫组的肺IgA和IgG反应总体相当,表达Pre-F抗原的VLP在脾脏中诱导产生更高水平的干扰素-γ(IFN-γ)。VLP免疫小鼠肺中嗜酸性粒细胞和产生白细胞介素-4(IL-4)的CD4 T细胞群体的频率显著降低,PreF+G疫苗可使CD4和CD8 T细胞显著增加。VLP免疫显著降低了小鼠肺中的病毒滴度和炎症,Pre-F+G VLP提供了最佳保护。总之,我们目前的研究表明,Pre-F+G VLP可能是一种针对RSV感染的潜在疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0dd/10051362/770b9dde2449/pharmaceutics-15-00782-g001.jpg

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