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含呼吸道合胞病毒G蛋白串联重复基因的病毒样颗粒疫苗诱导的保护作用。

Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein.

作者信息

Kim Ah-Ra, Lee Dong-Hun, Lee Su-Hwa, Rubino Ilaria, Choi Hyo-Jick, Quan Fu-Shi

机构信息

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.

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

出版信息

PLoS One. 2018 Jan 16;13(1):e0191277. doi: 10.1371/journal.pone.0191277. eCollection 2018.

DOI:10.1371/journal.pone.0191277
PMID:29338045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5770062/
Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants, young children and the elderly. However, there is no licensed vaccine available against RSV infection. In this study, we generated virus-like particle (VLP) vaccine and investigated the vaccine efficacy in a mouse model. For VLP vaccines, tandem gene (1-780 bp) for V1 VLPs and tandem repeat gene (repeated 450-780 bp) for V5 VLPs were constructed in pFastBacTM vectors, respectively. Influenza matrix protein 1 (M1) was used as a core protein in the VLPs. Notably, upon challenge infection, significantly lower virus loads were measured in the lung of mice immunized with V1 or V5 VLPs compared to those of naïve mice and formalin-inactivated RSV immunized control mice. In particular, V5 VLPs immunization showed significantly lower virus titers than V1 VLPs immunization. Furthermore, V5 VLPs immunization elicited increased memory B cells responses in the spleen. These results indicated that V5 VLP vaccine containing tandem repeat gene protein provided better protection than V1 VLPs with significantly decreased inflammation in the lungs. Thus, V5 VLPs could be a potential vaccine candidate against RSV.

摘要

呼吸道合胞病毒(RSV)是婴幼儿和老年人下呼吸道疾病的主要病因。然而,目前尚无针对RSV感染的许可疫苗。在本研究中,我们制备了病毒样颗粒(VLP)疫苗,并在小鼠模型中研究了疫苗的效力。对于VLP疫苗,分别在pFastBacTM载体中构建了用于V1 VLP的串联基因(1 - 780 bp)和用于V5 VLP的串联重复基因(重复450 - 780 bp)。流感基质蛋白1(M1)用作VLP中的核心蛋白。值得注意的是,在攻毒感染后,与未免疫小鼠和福尔马林灭活RSV免疫的对照小鼠相比,用V1或V5 VLP免疫的小鼠肺中测得的病毒载量显著降低。特别是,V5 VLP免疫显示出的病毒滴度明显低于V1 VLP免疫。此外,V5 VLP免疫引发脾脏中记忆B细胞反应增加。这些结果表明,含有串联重复基因蛋白的V5 VLP疫苗比V1 VLP提供了更好的保护,肺部炎症显著减轻。因此,V5 VLP可能是一种潜在的抗RSV疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/68bb9092a9c7/pone.0191277.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/4bd887adc314/pone.0191277.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/dbe95b6f4ec5/pone.0191277.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/2675d23889e0/pone.0191277.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/aa660b5e3f84/pone.0191277.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/6638b0659159/pone.0191277.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/395b1583d4a1/pone.0191277.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/68bb9092a9c7/pone.0191277.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/4bd887adc314/pone.0191277.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/2c50c889c22e/pone.0191277.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/dbe95b6f4ec5/pone.0191277.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/2675d23889e0/pone.0191277.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/aa660b5e3f84/pone.0191277.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/6638b0659159/pone.0191277.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8570/5770062/68bb9092a9c7/pone.0191277.g008.jpg

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