Recombinant CSFV E2 Protein Deletion for Serological Differentiation
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Solution Overview
Problem
Current classical swine fever virus (CSFV) vaccines do not allow for differentiation between infected and vaccinated animals, leading to challenges in trade restrictions and control of CSFV outbreaks, and existing DIVA vaccines have limitations in efficacy and specificity, especially in regions where other pestiviruses circulate.
Innovation Solution
A recombinant CSFV with a deletion of at least one amino acid in the TAVSPTTLR domain of the E2 protein is developed, which enables serological differentiation between infected and vaccinated animals, using a peptide-based diagnostic test, and is designed to be specific to CSFV without cross-reactivity with other pestiviruses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a CSFV vaccine is used to provide immunity, then protection against virulent CSFV is achieved, but serological differentiation between infected and vaccinated animals becomes impossible
Solution Approach 1:
The patent extracts the TAVSPTTLR epitope sequence from the E2 protein of the vaccine virus by introducing a deletion or substitution mutation. This allows the vaccine to maintain immunogenicity while creating a detectable difference between vaccinated and infected animals through serological testing.
Solution Approach 2:
The mutation is introduced at a specific local region (the TAVSPTTLR epitope domain) of the E2 protein rather than altering the entire protein structure. This localized modification preserves overall vaccine efficacy while enabling differentiation through specific antibody response detection.
2Measurement precision
If existing DIVA vaccines are used to enable differentiation, then serological differentiation is possible, but cross-reactivity with other pestiviruses occurs reducing specificity
Solution Approach 1:
The patent targets a specific local region (TAVSPTTLR epitope) within the E2 protein that is conserved among CSFV strains but variable in other pestiviruses. This localized approach enables specific detection of CSFV infection without cross-reactivity with BVDV or BDV.
Solution Approach 2:
The patent exploits sequence parameter differences in the TAVSPTTLR region among pestivirus species. By designing the vaccine and diagnostic test around this specific sequence variable, the system achieves high specificity for CSFV while maintaining the ability to differentiate vaccinated from infected animals.
3Measurement precision
If the TAVSPTTLR domain is modified to enable differentiation, then DIVA capability is achieved, but immune response efficacy may be reduced
Solution Approach 1:
The mutation is confined to the TAVSPTTLR epitope domain while preserving the rest of the E2 protein structure and other immunodominant regions. This localized modification maintains overall immunogenicity and protective immunity while enabling serological differentiation.
Solution Approach 2:
The patent uses subtle parameter changes (deletion or substitution of specific amino acids in TAVSPTTLR) rather than drastic modifications. These minimal changes are sufficient to prevent antibody cross-reactivity with the vaccine strain while preserving the immunogenicity needed for protective immunity.
Data Source
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Figure 3A~3B
AI summary
The invention relates to a recombinant classical swine fever virus (CSFV). A preferred recombinant CSFV comprises a deletion of at least one amino acid in a "TAVSPTTLR" domain of the E2 protein. The invention further relates to a vaccine comprising the recombinant CSFV, a method for generating a recombinant CSFV, and use of a recombinant CSFV.