Mutant PspA Protein Stability at Neutral pH
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Solution Overview
Problem
Existing pneumococcal vaccines based on polysaccharides have low immunogenicity, particularly in children, and fail to induce mucosal immunity, while D39-derived PspA is prone to deamination at neutral pH, affecting its stability and safety.
Innovation Solution
A mutant PspA protein with a specific mutation at position 254 (Asn to Asp) is developed, which maintains stability and antigenicity, and is capable of inducing both systemic and mucosal immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If D39 strain-derived PspA is used as a vaccine antigen, then high antigenicity and ability to induce neutralizing antibodies are achieved, but the protein is easily deaminated around neutral pH range, affecting stability and safety
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence at position 254 from asparagine (Asn) to aspartic acid (Asp). This chemical parameter change in the protein structure prevents deamination while maintaining the antigenic properties, thereby resolving the contradiction between antigenicity and molecular stability at neutral pH
2Reliability
If polysaccharide-based vaccines are administered via intramuscular injection, then systemic anti-IgG antibodies are induced, but mucosal immune response to pneumococci cannot be induced
Solution Approach 1:
The patent applies universality by designing a PspA-based vaccine that can simultaneously induce both systemic and mucosal immune responses. The modified PspA protein serves multiple functions: it maintains high antigenicity for systemic antibody production while also being capable of inducing mucosal immunity, thereby eliminating the limitation of polysaccharide vaccines
3Ease of operation
If T cell-independent polysaccharide vaccines are used, then vaccine administration is simplified, but low immunogenicity results in hardly inducing immune response to children
Solution Approach 1:
The patent applies parameter changes by transforming the vaccine from T cell-independent polysaccharide type to T cell-dependent protein type through amino acid sequence modification. This changes the immunological parameters to achieve high immunogenicity in children while maintaining ease of administration
Data Source
AI summary
The present invention provides D39-derived mutant PspA that does not undergo deamination and maintains stability as a molecule even around neutral pH range.Specifically, the present invention relates to a protein of the following (a) or (b):(a) a protein comprising the amino acid sequence as set forth in SEQ ID NO: 2 and having pneumococcal vaccine antigenic activity, and a protein substantially identical to the protein; or(b) a protein being a part of the amino acid sequence as set forth in SEQ ID NO: 2, wherein aspartic acid at position 254 is comprised in the part, and having pneumococcal vaccine antigenic activity, and a protein substantially identical to the protein.