Modulating Viral Immunosuppression via Polypeptide Sequence Substitution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccines and immunotherapy approaches for viral infections face challenges due to the immunosuppressive properties of retroviral envelope proteins, which can inhibit the host's immune response, making it difficult to elicit an effective immune response without altering their antigenic and infectious properties.
Innovation Solution
Development of polypeptides with specific amino acid sequences, such as X1-(Y)3-C-(Y)1-X2, that modulate the immunosuppressive properties of viral proteins while retaining their antigenic properties, allowing for the generation of immunogenic compositions and attenuated viruses to promote an efficient immune response against viral infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If retroviral envelope proteins are used in vaccines or immunotherapy, then antigenic properties are maintained, but immunosuppressive properties inhibit the host's immune response
Solution Approach 1:
The envelope protein is divided into functional domains, with the immunosuppressive domain (ISU) identified and separated from the antigenic domains. This segmentation allows selective modification of the ISU region while preserving antigenic regions, thereby maintaining vaccine efficacy while reducing immunosuppression
Solution Approach 2:
Amino acid substitutions are introduced in the immunosuppressive domain (e.g., changing specific residues in the ISU region) to alter the protein's immunosuppressive parameters. These parameter changes reduce immunosuppressive activity while maintaining the protein's antigenic structure and immune recognition capabilities
2Object-generated harmful factors
If the envelope protein sequence is modified to reduce immunosuppression, then immune response is enhanced, but antigenic properties may be altered
Solution Approach 1:
Modifications are localized specifically to the immunosuppressive domain (ISU) while leaving antigenic domains unchanged. This local quality approach ensures that antigenic properties remain stable and recognizable to the immune system, while only the immunosuppressive function is altered through targeted amino acid substitutions in specific regions
3Reliability
If the immunosuppressive domain is completely removed, then immune response is maximized, but viral infectivity and antigenic properties are lost
Solution Approach 1:
The immunosuppressive domain is extracted or removed from the envelope protein structure, creating a modified protein that retains antigenic and infectious properties without the harmful immunosuppressive function. This extraction allows the use of the envelope protein in vaccines and immunotherapy without the constraint of immunosuppression
Solution Approach 2:
The immunosuppressive domain, which originally served to protect the virus from immune detection, is converted into a beneficial target for modification. By removing or altering this domain, the harmful effect is transformed into an opportunity to create safer, more effective vaccines that can elicit strong immune responses without being suppressed
Data Source
AI summary
The present invention relates to a polypeptide having a sequence of 7 to 20 amino acid residues, which is capable of modulating the immunosuppressive properties of a viral protein or a fragment thereof, against the host in which it is expressed (immunosuppression-modulatory sequence) when it substitutes the homologous sequence of the viral protein or fragment, the polypeptide including the minimum following consensus amino acid sequence:X1Y9Y10Y11CY12X2 wherein, X1 and X2 are selected to impact on the immunosuppressive properties, and Y9 to Y12 represent variable amino acid residues.