Characterization of Bronchiolitis and Vaccine-induced Enhanced Respiratory Disease in Syrian Hamsters Caused by Respiratory Syncytial Virus Infection.

Abstract

Background: Respiratory syncytial virus (RSV) poses a considerable health burden to pediatric and elderly populations, but vaccine development is hindered by the risk of enhanced respiratory disease (ERD) and limitations of current animal models.

Methods: Syrian hamsters of different ages were intranasally inoculated with RSV to establish an age-stratified model. Additionally, old hamsters were immunized with heat-inactivated RSV (HI-RSV) for ERD research. Disease pathogenesis was assessed through symptom monitoring, viral load quantification, histopathological examination, and transcriptomic analysis.

Results: RSV infection induced coughing-like symptoms in adult and old hamsters. Neonates exhibited significant growth retardation, the most pronounced viral replication and delayed viral clearance, and prolonged bronchiolitis-like lung injury. HI-RSV vaccination in old hamsters resulted in classic ERD, characterized by enhanced lung pathology, eosinophil infiltration, and mucus overproduction. Further transcriptomic profiling revealed upregulation of pathways related to Th1/Th2 cell differentiation, with marked increases in Th2 cytokines (Il4, Il5, and Il13) and associated transcription factors (Jak3, GATA binding protein 3, and Runt-related transcription factor 3), mechanistically linking Th2-biased immunity to ERD.

Conclusions: Our findings confirm the relevance of using Syrian hamsters to study age-dependent RSV pathogenesis and to evaluate the safety of RSV vaccines, particularly with regard to the risk of ERD associated with Th2-biased immune responses.