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| Establishment and analysis of a murine model for respiratory syncytial virus vaccine-enhanced disease |
| JIA Ran1, LU Lu2, LIANG Xiaozhen3, SUN Zhiwu2, TAN Lingbing3, XU Menghua1, SU Liyun1, XU Jin1 |
| 1. Department of Clinical Laboratory, Children’s Hospital of Fudan University, Shanghai 201102, China; 2. Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; 3. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200032, China |
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Abstract Respiratory syncytial virus (RSV) is the most important pathogen responsible for children’s severe lower respiratory tract infection worldwide. As inactivated RSV vaccine could lead to RSV vaccine-enhanced disease (RVED)，no safe RSV vaccine has been permitted in clinical use yet, and the mechanism of RVED is still unclear. The aim of the present study is to establish a murine model that can steadily mimic the performance of RVED. A total of 30 BALB/c mice were divided into three groups and vaccinated with formalin-inactivated RSV (FV group), live RSV (VV group) or sterilized phosphate buffered saline (PBS) (BV group), respectively. Four weeks later, all the mice were challenged with live RSV intranasally. The bodyweight of the tested animals was measured on the day of viral challenge and the following 3 days. T cell immune response, lung RSV load and pulmonary pathology were detected by flow cytometry, quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) and lung hematoxylin-eosin (HE) staining respectively. Compared with the VV group and the BV group, the bodyweight of the mice in the FV group showed the largest weight loss after challenge. Severe pneumonia with extensive lymphocytic and eosinophilic infiltration could be seen in the FV group only. Lung RSV load in the FV group was the lowest. The number of CD4＋ T cells in the FV group was higher than those in the other two groups, while the number of CD8＋ T cells showed no significant difference among the three groups. The secretion of interleukin 4 (IL-4) in CD4＋ T cells and IL-4/interferon γ (IFN-γ) ratio in the FV group were much higher than those in the other two groups, while the secretions of tumor necrosis factor α (TNF-α) and IFN-γ in the FV group were much lower than those in the VV group. In conclusion, a murine model of RVED has been established successfully, showing an unbalanced Th2-biased immune response and impaired CD8＋ T cell function. The model could be used to help the study of RVED and development of protective and safe RSV vaccines.
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Received: 26 February 2016
Published: 25 June 2016
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Corresponding Authors:
XU Jin
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2016, Vol. 11 
