Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR/Cas9 technology. Rag2−/− mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 109.8 copies/g and 1c106 TCID50 in nasal cavity, as well as 1 × 108 copies/g and 1 × 105 TCID50 in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2−/− mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2−/− mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics.
Human respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract infections in infants and immunocompromised populations, causing approximately 160,000 annual deaths globally. Despite recent approvals of prefusion F (pre-F) protein-based vaccines (Arexvy, Abrysvo) for older adults and pregnant women, pediatric vaccine development faces unique challenges including enhanced respiratory disease (ERD) risks, maternal antibody interference, and immature infant immune responses. Meanwhile, G protein glycosylation variability and NS1/NS2-mediated interferon suppression remain the outstanding difficulties in structure-based vaccine design. Additionally, current animal models demonstrate notable constraints in virus replication, host susceptibility, immune responses, clinical symptoms, and ERD phenomena. This review synthesizes current obstacles and innovative strategies, highlighting that the selection of multi-antigen strategies, appropriate adjuvants, and the development of more precise preclinical animal models are critical elements that will determine the efficacy and safety of future RSV vaccines.
In recent years, the rapid development of geographic information system technology and the popularity of geo-location-based mobile information services have made people pay more attention to geography-related information. Thus, the information retrieval and related services based on geographic has a broad application prospects. However, the traditional search engine for the processing of geographic information seems powerless. Geographic Information Retrieval (GIR) is a kind of retrieval technique which is concerned with geographic information. A geographic knowledge base (GKB) has a key role in GIR, it can provides support for query disambiguation, query term expansion, relevance ranking, document annotation, and reasoning about geographical concepts. In this paper, we construct a GIR-oriented geographic knowledge base based on Chinese Wikipedia named NCGKB. First, we give the overall structure and design the geographic ontology. On the basis of the ontology and taking advantage of characteristics of Wikipedia pages, three extractors were developed to extract geographic entities, entity attributes and entity relations. For the geographic relation extraction, a geographic relation extraction method based on pattern matching was proposed which can effectively extract relations from content of Chinese Wikipedia. Finally, experimental results verify the effectiveness of the relationship extraction.