CSFV E2 Protein TAV Epitope Substitutions
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Solution Overview
Problem
Current vaccines for classical swine fever (CSFV) lack stability in marker epitopes, making it difficult to differentiate between vaccinated and infected animals, and existing substitutions are not suitable for generating stable modified live vaccines.
Innovation Solution
A CSFV vaccine with specific amino acid substitutions in the TAV epitope of the E2 protein, such as proline to lysine at position 144 and threonine to aspartic acid at position 145, which remains stable after multiple passages in cell culture and re-isolation from vaccinated animals, allowing for effective differentiation between vaccinated and infected animals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing substitutions in the TAV epitope are used, then vaccine differentiation capability is improved, but stability after multiple passages deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically testing different amino acid substitutions at positions 144 and 145 of the TAV epitope (proline/threonine to various alternatives). Through this parameter variation approach, the invention identified that substitutions to aspartic acid and lysine specifically provide both differentiation capability and stability, resolving the contradiction between measurement precision and stability.
2Reliability
If a stable marker epitope is achieved, then reliability of vaccine differentiation is improved, but device complexity increases due to multiple amino acid substitutions
Solution Approach 1:
The patent applies local quality by making targeted amino acid substitutions specifically at positions 144 and 145 within the TAV epitope, rather than modifying the entire E2 protein or virus structure. This localized approach achieves reliable differentiation while minimizing overall complexity, as only two specific residues are modified out of the entire epitope sequence.
Data Source
AI summary
The present invention relates i.a. to a CSFV (classical swine fever virus) comprising a substitution of proline to lysine at amino acid position 44 of the E2 protein and a substitution of threonine to aspartic acid at amino acid position 45 of the E2 protein. Further, the present invention provides an immunogenic composition comprising the CSFV of the present invention and the use of the immunogenic composition for reducing the incidence of or severity in an animal of one or more clinical signs associated with CSF. Moreover, the present invention provides a method of differentiating animals infected with CSFV from animals vaccinated with the immunogenic composition of the present invention.