BVDV Immunogenic Compositions Using Conserved CD8+ T Cell Epitopes
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Solution Overview
Problem
Current BVDV vaccines face challenges due to antigenic diversity and hypervariable neutralizing epitopes, leading to limited efficacy in protecting against both BVDV-1 and BVDV-2 strains, and there is a need for a more broadly protective vaccine to manage Bovine Respiratory Disease (BRD) effectively.
Innovation Solution
Development of a CTL-based vaccine incorporating BVDV-specific CD8+ T cell epitopes, identified through proteome-wide computational analysis, targeting conserved regions of the BVDV polyprotein, including E2 and NS3 antigens, to prime potent and sustained cross-protective immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional MLV and KV vaccines are used, then BVDV-specific antibody and CD4+ T cell responses are elicited, but protection against diverse BVDV strains is limited due to antigenic diversity and hypervariable neutralizing epitopes
Solution Approach 1:
The patent extracts and focuses on CD8+ T cell epitopes from conserved regions of BVDV structural and nonstructural proteins, specifically targeting epitopes that are preserved across different genotypes and subgenotypes. This extraction approach allows the vaccine to provide broad protection by concentrating on the most conserved viral regions rather than attempting to cover all variable epitopes.
Solution Approach 2:
The vaccine composition is designed to elicit universal CD8+ T cell responses against multiple BVDV strains simultaneously. By incorporating epitopes from both structural (E2) and nonstructural (NS3, NS4A-B, NS5A-B) proteins, the vaccine provides multi-functional protection across different viral genotypes, making it effective against a broad spectrum of BVDV strains.
2Reliability
If MLV vaccine is used, then BVDV-specific CD8+ T cells are induced which provides enhanced efficacy, but safety-related issues arise
Solution Approach 1:
The patent extracts only the essential immunogenic components (specific CD8+ T cell epitopes) from the viral genome, separating these from the rest of the viral structure. This extraction allows the vaccine to provide protective immunity without containing live virus, thereby eliminating safety concerns associated with MLV vaccines while maintaining the ability to induce CD8+ T cell responses.
Solution Approach 2:
The vaccine uses synthetic or recombinant copies of specific viral epitopes rather than live virus. These copies are designed to mimic the immunogenic properties of the actual virus without possessing viral replication capabilities, thus providing protective immunity while avoiding the safety issues inherent in live virus vaccines.
3Adaptability or versatility
If vaccine targeting conserved regions is developed, then broad protection against multiple strains is achieved, but identification of epitopes requires complex computational analysis
Solution Approach 1:
The patent performs preliminary computational analysis to identify and select the most conserved CD8+ T cell epitopes before vaccine formulation. By pre-identifying epitopes from conserved regions of BVDV proteins and validating their immunogenicity in advance, the vaccine can be designed to provide broad protection without requiring complex analysis during the actual vaccine development or deployment phases.
Data Source
AI summary
The present disclosure provides an immunogenic composition and methods of treating, preventing, and reducing the duration, incidence, and/or severity of clinical signs or symptoms of BVDV infection. The immunogenic composition includes at least one bovine MHC I-binding peptide. In some forms, the immunogenic composition includes a BPI3Vc vector expressing at least an antigenic CD8+ T cell epitope derived from at least one bovine viral diarrhea virus (BVDV) antigen selected from the group consisting of Npro, Erns, E1, E2, NS2-3, NS4A-B, NS5A-B, and any combination thereof.