Development of a HEp2‐CDX Mouse Model With Sustained High RSV Viral Loads for Robust Antiviral Therapeutic Evaluation

The respiratory syncytial virus (RSV) is a predominant pathogen that causes lower respiratory tract infections and is widespread among infants and the elderly. Antibodies and antiviral drugs are effective treatment strategies for RSV, but their efficacy varies among different animal models. Here, we present a mouse model constructed using HEp-2 cell line-derived xenograft (HEp2-CDX) technology. The HEp2-CDX mouse model sustained high viral loads following both intratumoral and intravenous inoculation with RSV. The average peak titers rapidly reached 1 × 107 copies/g in lung tissues and 6 × 109 copies/g in the tumor tissues over a period up to 5 days. Furthermore, the addition of a clinical monoclonal antibody (nirsevimab) and an antiviral drug (ziresovir) showed strong antiviral activity within this animal model. These findings suggest that HEp2-CDX mice, which enable stable RSV infection and replication, serve as useful models for evaluating antiviral therapeutics.