An adult gerbil model for evaluating potential coxsackievirus A16 vaccine candidates
| Autor: | Chong-Gao Hu, Zhi-Yao Xu, Chen-hui Yao, Shichang Xia, Zi-An Mao, Jianmin Jiang, Yong Xia, Zhang-Nv Yang, Meng Gao, Pingping Yao, Han-ning Ying, Yisheng Sun, Hang-Jing Lu, Zi-Ping Miao, Zhi-yong Zhu, Hanping Zhu, Fang Xu, Hai-qing Xiang, Chen Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Male
030231 tropical medicine Gerbil Pathogenesis 03 medical and health sciences 0302 clinical medicine Paralysis Medicine Animals 030212 general & internal medicine Alum adjuvant Myositis Enterovirus General Veterinary General Immunology and Microbiology business.industry Public Health Environmental and Occupational Health Viral Vaccines Viral Load medicine.disease Antibodies Neutralizing Vaccination Disease Models Animal Infectious Diseases Animals Newborn Vaccines Inactivated Inactivated vaccine Immunology Molecular Medicine Female medicine.symptom business Gerbillinae Viral load |
| Zdroj: | Vaccine. 37(36) |
| ISSN: | 1873-2518 |
| Popis: | A suitable animal model of CVA16 infection is crucial in order to understand its pathogenesis and to help develop antiviral vaccines or screen therapeutic drugs. The neonatal mouse model has a short sensitivity period to CA16 infection, which is a major limitation. In this study, we demonstrate that adult (60-day-old) gerbils are susceptible to CVA16 infection at high doses (108.0 TCID50). A clinical isolate strain of CVA16 was inoculated intraperitoneally into adult gerbils, which subsequently developed significant clinical symptoms, including hind limb weakness, paralysis of one or both hind limbs, tremors, and eventual death from neurological disorders. Real-time RT-PCR revealed that viral loads in the spinal cord and brainstem were higher than those in other organs/tissues. Histopathological changes, such as neuronal degeneration, neuronal loss, and neuronophagia, were observed in the spinal cord, brainstem, and heart muscle, along with necrotizing myositis. Gerbils receiving both prime and boost immunizations of alum adjuvant inactivated vaccine exhibited no clinical signs of disease or mortality following challenge by CVA16, whereas 80% of control animals showed obvious clinical signs, including slowness, paralysis of one or both hind limbs, and eventual death, suggesting that the CVA16 vaccine can fully protect gerbils against CVA16 challenge. These results demonstrate that an adult gerbil model provides us with a useful tool for studying the pathogenesis and evaluating antiviral reagents of CVA16 infection. The development of this animal model would also be conducive to screening promising CVA16 vaccine candidates as well as further vaccination evaluation. |
| Databáze: | OpenAIRE |
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