Identification and use of nucleocapsid protein targeting molecules that protect animals against crimean-congo hemorrhagic fever virus

The monoclonal antibody mAb-9D5 targets the nucleocapsid protein of CCHFV, offering significant protection against the virus by delaying symptom onset and improving survival in mouse models, addressing the lack of effective treatments for CCHFV infections.

WO2025059654A2 Publication Date: 2025-03-20UNITED STATES OF AMERICA THE AS REPRESENTED BY THE SEC OF THE ARMY
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Patent Information

Application Number
PCT/US2024/046918
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-09-15
Filing Date
2024-09-16
Publication Date
2025-03-20

AI Technical Summary

Technical Problem

There are no licensed therapeutics or vaccines available to prevent or treat Crimean-Congo hemorrhagic fever virus (CCHFV) infections, highlighting the need for effective anti-CCHFV products that can provide both prophylactic and post-exposure protection.

Method used

Development of a molecule targeting the nucleocapsid protein of CCHFV, specifically a non-neutralizing murine monoclonal antibody called mAb-9D5, which has been shown to provide significant protection in mouse models by delaying the onset of severe symptoms and improving survival rates.

Benefits of technology

mAb-9D5 demonstrates protective efficacy against CCHFV by delaying liver injury, preserving Kupffer cells, and reducing inflammatory cell infiltration, thereby extending survival and reducing disease severity in infected mice.

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Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is an endemic and emerging virus and a WHO priority pathogen, and thus medical countermeasures such as antibodies that broadly protect against heterologous strains of CCHFV are in need to mitigate a severe disease caused by CCHFV. The nucleocapsid (N) protein of CCHFV is highly conserved between CCHFV strains, and it can function as a target of therapeutic treatment. In this disclosure, a molecule, in particular a monoclonal antibody-based molecule, against the N protein of CCHFV is provided, comprising a polypeptide having a heavy chain variable region, a polypeptide having a light chain variable region and / or a polypeptide having a heavy chain variable region and a light chain variable region, or fragment or variant thereof as well as a nucleotide comprising a nucleic acid strand encoding a heavy chain variable region, a nucleotide comprising a nucleic acid strand encoding a light chain variable region and / or a nucleotide comprising a nucleic acid strand encoding a heavy chain variable region and a light chain variable region.
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