Immunogenic Composition for Neisseria Meningitidis B Protection
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Solution Overview
Problem
Current vaccines against Neisseria meningitidis serogroup B are ineffective due to the polysaccharide capsule's poor immunogenicity and high variation in surface-exposed antigens, particularly for sequence type ST269, which is prevalent and causes significant disease in children and young adults.
Innovation Solution
Development of an immunogenic composition comprising a fusion protein combining N-terminal and C-terminal fragments of fHbp proteins from different families, along with additional antigens like TdfI, Hsf, or Hap, to generate a robust antibody response against Neisseria meningitidis ST269, providing protection against a wide range of invasive MenB clonal complexes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If vaccines are developed using capsular polysaccharide of serogroup B, then vaccine production is achieved, but the polysaccharide capsule is poorly immunogenic due to immunologic similarity to human neural cell adhesion molecule
Solution Approach 1:
The patent extracts the immunogenic problem by removing the poorly immunogenic capsular polysaccharide from the vaccine composition and replacing it with alternative antigens (fHbp, TdfI, Hsf, Hap) that can elicit protective immune responses without the self-tolerance issues of the native capsule
Solution Approach 2:
The patent changes the antigenic parameters of the vaccine by substituting the capsular polysaccharide antigen with protein-based antigens (fHbp, TdfI, Hsf, Hap) that have different immunological properties and can overcome the molecular mimicry problem
2Adaptability or versatility
If vaccines focus on surface exposed structures of the meningococcal outer membrane, then vaccine development progresses, but marked variation in these antigens among strains hamper effectiveness particularly against ST269
Solution Approach 1:
The patent creates a universal vaccine approach by selecting antigens (fHbp, TdfI, Hsf, Hap) that are conserved across multiple serogroups and sequence types, including ST269, thereby achieving broad-spectrum protection despite antigenic variation in traditional surface structures
Solution Approach 2:
The patent employs a composite antigen strategy by combining multiple different antigens (fHbp, TdfI, Hsf, Hap) in a single vaccine formulation to address the diversity and variation of Neisseria meningitidis strains, particularly ST269
3Ease of operation
If serogroup B is targeted with traditional vaccines, then vaccine administration is achieved, but only a transient antibody response of predominantly IgM isotype is induced
Solution Approach 1:
The patent changes the immunological response parameters by using protein-based antigens (fHbp, TdfI, Hsf, Hap) that can elicit sustained antibody responses with appropriate isotype distribution, overcoming the transient IgM-only response characteristic of traditional capsular polysaccharide vaccines
Data Source
AI summary
Compositions for the treatment or prevention of Neisserial infection and methods for their use and manufacture are provided herein.