Recombinant VSV Vector Encoding CCHFV-GPC Antigen
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current preventative treatments and diagnostic methods for Crimean-Congo Hemorrhagic Fever (CCHF) are inadequate, with no established virus-specific treatment and limited effectiveness of existing vaccines and therapies, posing a significant risk to individuals and armed forces operating in endemic areas.
Innovation Solution
Development of recombinant vesicular stomatitis virus vectors (ΔGrVSV) encoding Crimean-Congo Hemorrhagic Fever glycoprotein precursor (CCHFV-GPC) for use as a vaccine or therapeutic composition, which can induce an immune response and provide protection against lethal CCHFV challenge with a single injection, effective across multiple species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant vesicular stomatitis virus vectors encoding CCHFV-GPC are used as vaccine, then protective immunity is induced with single injection, but replication competence may pose safety risks
Solution Approach 1:
The patent uses a vesicular stomatitis virus (VSV) vector as an intermediary delivery system to transport and express the CCHFV-GPC antigen gene in host cells. The VSV vector acts as a safe mediator that can be engineered to be replication-deficient, eliminating the risk of live virus replication while still enabling effective antigen expression and immune response induction.
Solution Approach 2:
The patent modifies the replication status parameter of the viral vector by creating replication-deficient VSV mutants lacking essential viral genes (such as the L gene encoding RNA polymerase). This parameter change transforms the vector from potentially harmful replicating virus to safe non-replicating vector, while preserving its ability to deliver and express the protective CCHFV-GPC antigen.
2Ease of manufacture
If glycoprotein ectodomains or portions are used as recombinant construct, then vaccine candidate is produced, but effectiveness is limited to specific strain
Solution Approach 1:
The patent employs the full-length CCHFV glycoprotein precursor (GPC) that contains both GC and GN ectodomains in a single polypeptide. This universal antigen construction approach allows the vaccine to elicit broad immune responses against multiple CCHFV strains, overcoming the limitation of strain-specific effectiveness while maintaining ease of recombinant production through single-gene expression.
3Ease of manufacture
If inactivated antigen from suckling mouse brain preparations is used, then vaccine is generated, but it is unsuitable for FDA approval
Solution Approach 1:
The patent replaces the traditional mechanical/inactivation-based vaccine production method (using suckling mouse brain preparations and chemical inactivation) with a modern recombinant DNA technology approach. The CCHFV-GPC antigen is produced through genetic engineering in eukaryotic expression systems, eliminating the need for animal brain tissues and chemical inactivation processes, thereby achieving both ease of manufacture and FDA approval suitability.
Data Source
AI summary
Certain embodiments are directed generally to compositions and methods related to recombinant vesicular stomatitis virus vectors (ΔGrVSV) encoding Crimean-Congo Hemorrhagic Fever glycoprotein precursor (CCHFV-GPC) and forming a recombinant vesicular stomatitis virus vector encoding Crimean-Congo Hemorrhagic Fever glycoprotein precursor (ΔGrVSV-CCHFV-GPC).