Development of novel monoclonal antibodies for detection of pan-Lassa virus

Lassa virus (LASV), the causative agent of Lassa fever (LF), poses a significant public health concern in endemic regions due to its high morbidity and mortality. Rapid and accurate diagnosis is critical for effective clinical management and containment during LF outbreaks. However, the genetic diversity of LASV, encompassing at least seven distinct lineages, poses a major challenge for the development of broadly reactive diagnostic tools. Therefore, there is an urgent need to develop detection methods that are effective across diverse lineages. To address this challenge, we generated a panel of cross-reactive monoclonal antibodies (mAbs) targeting the LASV nucleoprotein (NP). Several mAbs exhibited broad reactivity across LASV lineages I-VII in different immunoassays such as enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence assay. Utilizing these broadly reactive mAbs, we developed an antigen-capture sandwich ELISA capable of detecting LASV NP from all seven lineages with high sensitivity. Our findings highlight a set of novel mAbs with broad cross-reactivity across lineage. In addition, we demonstrated their utility in a sandwich ELISA format for pan-LASV detection. This pan-LASV diagnostic approach offers a promising tool for improved LF diagnosis in both clinical and epidemiological settings.