Meningococcal fHbp Vaccine Broadens Strain Coverage
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Solution Overview
Problem
Current meningococcal vaccines lack effective coverage against serogroup B meningococcus, particularly due to poor protection offered by the M01573 fHbp sequence against strains like MC58, which represents over 30% of circulating family I strains, leading to inadequate strain coverage.
Innovation Solution
A vaccine composition that includes two fHbp antigens, one more closely related to MC58 and the other to M01573, or combines an fHbp antigen from family I with one from family III, to generate distinct immune responses and broaden strain coverage, using specific criteria for sequence selection and formulation, including adjuvants like aluminium salts, oil-in-water emulsions, and immunostimulatory oligonucleotides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If a single fHbp antigen (e.g., M01573 sequence) is used in the vaccine, then the vaccine composition is simple and easy to manufacture, but the strain coverage is insufficient particularly against MC58 and related strains
Solution Approach 1:
The patent combines multiple fHbp antigens from different families (Family I, Family II, and/or Family III) into a single vaccine composition. This merging of distinct antigenic components enables the vaccine to elicit immune responses against multiple meningococcal strains simultaneously, resolving the contradiction between formulation simplicity and broad strain coverage.
Solution Approach 2:
The vaccine composition is designed to serve multiple protective functions by including fHbp antigens from different families. Each antigen family targets different circulating strains, making the single vaccine formulation universally effective against diverse meningococcal serogroup B strains, including MC58, M01573, and other variants.
2Adaptability or versatility
If multiple fHbp antigens from different families are combined in the vaccine, then the strain coverage is broadened, but the vaccine complexity and formulation difficulty increase
Solution Approach 1:
The patent segments the fHbp antigen into distinct family categories (Family I, II, and III) with specific sequence identity criteria. This segmentation allows for systematic selection and combination of antigens based on defined parameters, managing the complexity through structured classification rather than arbitrary formulation.
Solution Approach 2:
The patent uses specific parameter thresholds (e.g., ≥75% sequence identity within a family, ≤70% identity between families) to guide antigen selection and combination. These quantitative parameters provide objective criteria for formulation, simplifying the decision-making process despite the multi-component nature of the vaccine.
3Ease of manufacture
If fHbp antigen from Family I (M01573 sequence) is used, then the vaccine can be produced with available sequences, but protection against MC58 strain is poor
Solution Approach 1:
The patent creates a composite antigen formulation by combining M01573 (Family I) with antigens from other families (II and/or III). This composite approach leverages the availability of M01573 while supplementing it with additional antigenic components that provide protection against MC58 and other strains, achieving both manufacturability and reliability.
Solution Approach 2:
The vaccine merges M01573-based Family I antigen with Family II and/or III antigens to create a multi-family formulation. This combination ensures that the benefits of available M01573 sequences are retained while adding complementary antigens that fill the protection gap against MC58 and related strains.
Data Source
AI summary
The M01573 sequence of meningococcal fHbp offers poor coverage in a vaccine. The invention addresses this poor coverage in two ways. In a first aspect, a fHbp-based vaccine includes two family I fHbp sequences, one which is more closely related to MC58 than to M01573, and vice versa. In a second aspect, a multi-family fHbp-based vaccine uses a family I fHbp sequence which is more closely related to MC58 than to M01573, in combination with a family III fHbp sequence.