HCMV gB Polypeptide Mutations for Vaccine Potency
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Solution Overview
Problem
Current HCMV vaccines and diagnostic reagents lack potency and durability, and there is a need for improved immunogenic compositions and therapeutic antibodies against cytomegalovirus infections, particularly targeting the gB envelope glycoprotein.
Innovation Solution
Development of modified polypeptides with mutations in the fusion loop 1, fusion loop 2, and furin-like cleavage site of the HCMV gB protein, which enhance antigenicity, structural integrity, and immune response, while reducing steric occlusion of neutralizing epitopes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If gB subunit vaccines are used, then safety is improved, but potency and durability of protection are insufficient
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid mutations in the fusion loops of gB polypeptide. These mutations alter the conformational dynamics and stability of the protein, enhancing its immunogenicity while maintaining safety. The modified polypeptides exhibit improved structural integrity and antigenicity, directly addressing the insufficiency of potency and durability in conventional gB subunit vaccines.
2Reliability
If mutations are introduced in fusion loops to enhance antigenicity, then immune response is improved, but structural integrity may be compromised
Solution Approach 1:
The patent applies local quality by introducing mutations specifically in the fusion loops (FL1 and FL2 regions) of the gB polypeptide while leaving the rest of the structure intact. This localized modification approach enhances antigenicity and immune response in the critical fusion loop regions without compromising the overall structural integrity of the gB protein. The mutations are strategically placed to optimize immunogenicity while preserving essential structural features.
3Stability of the object's composition
If wild-type gB polypeptide is used, then natural conformation is maintained, but steric occlusion of neutralizing epitopes occurs
Solution Approach 1:
The patent applies inversion by reversing the conventional approach: instead of trying to access epitopes in the wild-type conformation, the invention introduces mutations that proactively open up or reshape the fusion loops to expose neutralizing epitopes. This conformational remodeling eliminates steric occlusion and makes previously hidden epitopes accessible to antibodies, thereby enhancing vaccine efficacy.
Data Source
AI summary
The present invention relates to a polypeptide that includes at least one mutation in the fusion loop 1 region and/or in the fusion loop 2 region and/or in the furin-like cleavage site of a human cytomegalovirus gB polypeptide. In one embodiment, the polypeptide undergoes a structural conformation change in response to pH change.