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

Abstract

Respiratory syncytial virus (RSV) poses a considerable health burden to pediatric and elderly populations. Vaccine development has been historically challenged by the risk of enhanced respiratory disease (ERD), and existing animal models often fail to adequately recapitulate human disease. Syrian hamster were established as a translational model for studying age-stratified RSV infection and vaccine-associated ERD. Animals of different ages were intranasally inoculated with RSV. 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. 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, Il13) and associated transcription factors (Jak3, Gata3, Runx3), mechanistically linking Th2-biased immunity to ERD. 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.