An adult gerbil model for evaluating potential coxsackievirus A16 vaccine candidates |
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| Affiliation: | 1. Key Lab of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China;2. Zhejiang Pukang Biotechnology Co.,LTD., China;3. Zhejiang University, Hangzhou, China;4. China Medical University, Shenyang, China;5. Health Service Development Center of Hangzhou, Hangzhou, China;1. Department of Infectious Diseases, Italian National Institute of Health (ISS), Viale Regina Elena 299, 00161 Rome, Italy;2. Regional Directorate for Health and Social Policy, Lazio Region, Via R. Raimondi Garibaldi 7, 00145 Rome, Italy;3. Bambino Gesù Paediatric Hospital, Piazza Sant’Onofrio 4, 00165 Rome, Italy;4. Italian National Institute of Statistics (ISTAT), Via Cesare Balbo 16, 00184 Rome, Italy;1. Saint Louis University, Division of Infectious Diseases, Allergy, and Immunology, Department of Internal Medicine, 1100 S. Grand Blvd., Edward A. Doisy Research Center – 8th Floor, Saint Louis, MO 63104, United States;2. Saint Louis University, Department of Molecular Microbiology & Immunology, 1100 S. Grand Blvd., Edward A. Doisy Research Center – 8th Floor, Saint Louis, MO 63104, United States;3. EpiVax, Inc., 188 Valley Street, Suite 424, Providence, RI 02909, United States;4. University of Rhode Island, Institute for Immunology and Informatics, Department of Cell and Molecular Biology, 80 Washington Street, Providence, RI 02903, United States |
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| Abstract: | 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. |
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| Keywords: | Coxsackievirus A16 Animal model Gerbils Inactivated vaccine |
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