Characterization of bronchiolitis and vaccine-induced enhanced respiratory disease in Syrian hamsters caused by respiratory syncytial virus infection

Abstract

Respiratory syncytial virus (RSV) presents a significant health risk to pediatric and old populations. The quest for developing effective RSV vaccines and immunoprophylactic measures remains highly active, while the catastrophic enhanced respiratory disease (ERD) reaction triggered by RSV vaccines poses lingering concerns. Meanwhile, as the basis of vaccine research, the development of animal models of RSV infection has shown less substantial progress, with considerable disparities in immunological and pathological responses compared to humans. The Syrian hamster, which is reported to be susceptible to RSV infection, seems promising, but the lack of in-depth studies has hampered its application. Consequently, we have refined the RSV-infected hamster model by establishing infection models at different ages, reanalyzing virological and pathological data, and applying vaccination with heat-inactivated RSV virus for ERD reaction. In general, neonatal hamsters exhibited the highest level of viral amplification, while old hamsters displayed the most severe pathological manifestations, with adult hamsters in between. Although Syrian hamsters were moderately susceptible to RSV infection, they showed typical pathological changes of bronchitis in all age groups, with adult and old animals even showing clinical signs of coughing. In addition, hamsters demonstrated the typical ERD response to heat-inactivated virus, characterized by the exacerbation of lung injury with extensive neutrophil and eosinophil infiltration, as well as TH2 polarization. Collectively, these characteristics suggest that the Syrian hamster model has significant potential for investigating the pathogenesis of RSV infection, elucidating the mechanism of ERD, and evaluating vaccine efficacy and safety. ImportanceThe Syrian hamster has been shown in our study to be a potential model for respiratory syncytial virus (RSV) infection, according to the following characteristics: Hamsters of three different age groups all developed typical pulmonary bronchiolitis following RSV infection, whereas adult and old hamsters showed typical cough symptoms, comparable to those observed in clinical patients. Hamsters of different ages showed considerable variability. Neonatal hamsters tolerated more viral replication, while old hamsters suffered the most severe pulmonary pathology. Hamsters exhibited typical ERD responses after inoculation with heat-inactivated RSV virus, including enhanced lung pathology, pulmonary eosinophilic and neutrophil infiltration, and Th2 polarization, which was remarkable and more similar to the typical characteristics of the ERD response in humans.