fHbp Fusion Vaccine Composition With Reduced OMV Reactogenicity
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Solution Overview
Problem
Existing meningococcal vaccines, such as BEXSERO™, provide limited inter-variant cross-protection against diverse meningococcal strains and can cause fever when co-administered with routine infant vaccines.
Innovation Solution
A fusion polypeptide comprising all three variants (v1, v2, and v3) of meningococcal fHbp, combined with NHBA and/or NadA polypeptides and meningococcal outer membrane vesicles (OMVs) at specific concentrations, to enhance vaccine coverage and reduce adverse reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing meningococcal vaccines (e.g., BEXSERO) are used, then protection against specific serogroups is provided, but inter-variant cross-protection against diverse meningococcal strains is limited
Solution Approach 1:
The patent combines multiple fHbp variants (v1, v2, v3) into a single fusion polypeptide structure, merging the protective antigens from different variants into one molecule. This allows the vaccine to elicit antibodies that recognize multiple variants simultaneously, thereby improving inter-variant cross-protection while maintaining reliable protection coverage.
Solution Approach 2:
The fusion polypeptide is designed to perform multiple protective functions by incorporating different fHbp variants (v1, v2, v3) that target different meningococcal strains. This multi-functional antigen can provide broad-spectrum protection against diverse serogroup B strains, enhancing the vaccine's adaptability across different variants.
2Adaptability or versatility
If meningococcal vaccines are co-administered with routine infant vaccines, then comprehensive immunization is achieved, but fever reactions occur
Solution Approach 1:
The patent modifies the vaccine composition by using a fusion polypeptide with specific structural characteristics and controlled concentrations of components (e.g., OMVs at 5-30 μg/ml). These parameter changes in the antigen structure and formulation reduce the immunogenicity that triggers fever reactions while maintaining adequate protective immunity, allowing safe co-administration with routine infant vaccines.
3Adaptability or versatility
If a fusion polypeptide comprising all three fHbp variants is used, then broader protection against diverse strains is achieved, but vaccine composition complexity increases
Solution Approach 1:
Instead of formulating separate vaccines for each fHbp variant, the patent merges all three variants (v1, v2, v3) into a single fusion polypeptide. This consolidation simplifies the vaccine composition to one molecular entity that provides broad protection, reducing formulation complexity while maintaining extensive strain coverage.
Solution Approach 2:
The fusion polypeptide serves as a universal antigen that can protect against multiple variants simultaneously. This single multi-functional component replaces the need for multiple separate antigens, simplifying the vaccine composition while achieving broad-spectrum protection against diverse meningococcal strains.
Data Source
AI summary
Meningococcal vaccines can be improved by including multiple alleles or variants of fHbp, in order to provide broader coverage of the diversity which is known for this protein, and/or by reducing the quantity of an OMV component in each dose.