Heterologous HPV Vaccine Combination to Avoid Junction Epitopes
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Solution Overview
Problem
Current HPV vaccines are ineffective in treating existing HPV infections or HPV-associated cancers, and there is a risk of immune responses against junction-associated epitopes and self-antigens due to similar antigen arrangements in prime-boost vaccines.
Innovation Solution
A vaccine combination comprising a first vaccine with a specific arrangement of HPV antigens and a heat shock protein, and a second vaccine with differently arranged HPV antigens, administered in a heterologous prime-boost regimen, potentially with an immune checkpoint inhibitor, to enhance immunogenicity and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If the same vaccine is given multiple times as homologous boosts, then the manufacturing process is simple and consistent, but the immune response against junction-associated epitopes is enhanced, leading to impaired response against the target pathogen
Solution Approach 1:
The vaccine combination is segmented into two distinct components: a priming vaccine containing a first fusion protein with a specific antigen arrangement, and a boosting vaccine containing a second fusion protein with a different antigen arrangement. This segmentation allows each vaccine to target different epitopes, preventing immune response against junction-associated epitopes while maintaining manufacturing simplicity through standardized production processes for each component.
Solution Approach 2:
The patent applies asymmetry by deliberately designing the first and second fusion proteins with different antigen arrangements. The first fusion protein uses one specific arrangement of HPV antigens, while the second fusion protein uses a different arrangement. This asymmetric design ensures that the immune response is directed against the target pathogen antigens rather than against junction-associated epitopes that would be identical in both vaccines, thereby improving immune response quality while maintaining manufacturing consistency.
2Ease of manufacture
If fusion proteins with the same antigen arrangement are used in both priming and boosting vaccines, then the manufacturing process is simplified, but the immune system may develop cross-reactivity against self-antigens due to similarity between pathogenic elements and human proteins
Solution Approach 1:
The vaccine combination segments the antigen presentation into two distinct phases with different fusion protein arrangements. The priming vaccine presents a first arrangement of HPV antigens, while the boosting vaccine presents a second, different arrangement. This segmentation prevents the immune system from developing cross-reactivity against self-antigens that would occur with identical antigen arrangements in both vaccines, while maintaining manufacturing simplicity through standardized production for each component.
Solution Approach 2:
The patent employs asymmetry by designing the first and second fusion proteins with different antigen arrangements. This asymmetric design ensures that the immune response is directed against the target pathogen antigens rather than against junction-associated epitopes or self-antigens. The different arrangements prevent molecular mimicry between the vaccine antigens and human proteins, thereby reducing cross-reactivity while maintaining manufacturing consistency.
3Reliability
If heterologous prime-boost with different vectors is used, then both antibody and T cell immunity are enhanced, but the complexity of the vaccine regimen increases
Solution Approach 1:
The vaccine combination segments the immunization process into two distinct vaccines: a priming vaccine with a first fusion protein and a boosting vaccine with a second fusion protein. Each vaccine can be produced using standardized platforms, and the segmentation allows for different antigen arrangements that enhance both antibody and T cell immunity. The modular design simplifies the overall regimen by using well-established vaccine manufacturing processes for each component.
Solution Approach 2:
The patent applies parameter changes by modifying the antigen arrangement parameter between the two vaccines. The first fusion protein uses a specific arrangement of HPV antigens, while the second fusion protein uses a different arrangement. This parameter change (antigen arrangement) enables enhanced immune response without requiring fundamentally different vector systems, thereby maintaining manufacturing simplicity while improving immunogenicity.
Data Source
AI summary
A vaccine combination may include first and second vaccines. The first vaccine may include a first fusion protein or a first polynucleotide encoding the first fusion protein. The first fusion protein may include an E7 protein of HPV-16; an E7 protein of HPV-18; an E6 protein of HPV-16; an E6 protein of HPV-18; and a heat shock protein. The second vaccine may include second and third fusion proteins, or a second polynucleotide encoding the second and third fusion proteins. The second fusion protein may include an E6 protein of HPV-16 and an E7 protein of HPV-16. The third fusion protein may include an E6 protein of HPV-18 and an E7 protein of HPV-18. A functional variant may be employed for one or more of the proteins. An amino acid sequence of junction regions in the first fusion protein may be different from those in the second and third fusion proteins.