Development of virus-specific anti-NS1 antibodies for use in neurotropic flavivirus NS1 antigen capture-based diagnostics

Project Details

Description

Rationale and positioning with regard to the state-of-the-art
Novelty: Due to increasing travel between endemic and non-endemic areas, the adaptation of mosquito vectors to new habitats, and the lack of effective early detection and prevention systems, arthropod-borne flaviviruses are spreading globally, including in Europe. West Nile virus (WNV), Tickborne encephalitis virus (TBEV), and Usutu virus (USUV) are spreading rapidly across Europe, facilitated by the fact that these viruses are transmitted by Culex mosquitoes (WNV, USUV) and Ixodes ticks (TBEV) which are found across large parts of the continent. Another Culex-borne virus causing very similar neurotropic symptoms and disease is the Japanese Encephalitis virus (JEV). Being able to discern between the different neurotropic flaviviruses present in a specific geographical zone is becoming crucial since early and accurate diagnosis of flavivirus infection and detailed epidemiological studies can improve the prevention and clinical management of the infection. The antigenic similarities and co-circulation in the same geographic areas make specific diagnoses challenging with the diagnostic methods currently available. The viral Non-structural protein 1 (NS1) has been identified as an auspicious biomarker because its presence in the blood can be detected at the onset of symptoms, and an antigen capture-based assay based on NS1 could be suitable for an application also in low-income countries where complex and expensive equipment cannot be utilized.
Gap: NS1 antigen capture-based assays are not commercially available for diagnosing JEV, WNV, TBEV, and USUV, predominantly due to the lack of specific monoclonal antibodies against NS1 of one flavirus that doe not cross-react with other flaviviruses. Indeed, NS1 similarities between flaviviruses, especially if they belong to the same serocomplex, can lead to a cross-reactivity that complicates their distinction.
Aim: The project aims to produce highly-specific monoclonal antibodies (mAbs) for the NS1 protein of WNV, JEV, TBEV, and USUV that can be used for diagnostics of these flaviviruses, excluding the possibility of cross-reactivity. The monoclonal antibodies will be generated using a subtractive immunization strategy, by which it is possible to obtain mAbs that can precisely discriminate between closely related proteins. Then mAb specificity will be tested and validated for use in the diagnosis of flavivirus infection. The production of this unique pool of mAbs will permit the development of innovative diagnostic tools that can drastically improve flavivirus infection diagnosis.
StatusActive
Effective start/end date29/05/24 → …

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