Chimeric fHBP Polypeptides for Cross-Strain Meningococcal Protection
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Solution Overview
Problem
Current vaccines against Neisseria meningitidis serogroup B fail to provide cross-strain protection due to the family specificity of the meningococcal factor H binding protein (fHBP), limiting their effectiveness across different strains of the bacteria.
Innovation Solution
Development of modified fHBP polypeptides that include specific amino acid sequences, such as SEQ ID NO: 76, which induce bactericidal antibodies capable of targeting all three fHBP families, thereby enhancing cross-family protection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If vaccines use surface-exposed proteins from outer membrane vesicles, then serum bactericidal antibody responses are elicited and protection against disease is achieved, but cross-strain protection is not induced
Solution Approach 1:
The patent creates hybrid fHBP polypeptides that incorporate amino acid sequences from multiple fHBP families (I, II, and III) into a single chimeric protein. This multi-family construct expresses epitopes recognized by antibodies against all three families simultaneously, enabling a single vaccine to provide cross-strain protection across diverse meningococcal strains that would otherwise require multiple separate vaccines.
2Adaptability or versatility
If separate fHBP families are expressed and purified to achieve cross-strain protection, then coverage across families I, II and III is increased, but the complexity of expression and purification increases
Solution Approach 1:
The patent merges the antigenic determinants of multiple fHBP families into a single hybrid polypeptide construct. By fusing amino acid sequences from families I, II, and III into one chimeric protein, the invention consolidates what would require three separate expression and purification processes into a single production workflow, thereby reducing manufacturing complexity while maintaining broad cross-strain coverage.
3Adaptability or versatility
If fHBP sequences are modified using mutagenesis-based approaches, then coverage across families is increased, but the specificity of protection remains limited to intra-family cross-protection
Solution Approach 1:
The patent constructs hybrid fHBP polypeptides that function as composite antigens, integrating conserved epitopic regions from multiple fHBP families into a single molecular entity. This composite approach ensures that antibodies generated against the hybrid protein recognize conserved structures across all three families, providing reliable inter-family cross-protection that simple mutagenesis of single-family proteins cannot achieve.
Data Source
AI summary
fHBP is a protein in Neisseria meningitidis. Three families of fHBP are known. To increase the ability of a fHBP protein to elicit antibodies that are cross-reactive between the families, fHBP is selected or engineered to have a sequence which can elicit broad-spectrum bactericidal anti-meningococcal antibodies after administration to a host animal.