Chimeric Dengue E Glycoprotein for Broad Neutralizing Antibody Response
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Solution Overview
Problem
Current dengue virus vaccines face challenges in eliciting long-lasting protective antibody responses against all four serotypes, with mechanisms of serotype 4 neutralization by human antibodies poorly understood, and existing vaccines often induce non-neutralizing antibodies, increasing the risk of dengue hemorrhagic fever upon subsequent exposure.
Innovation Solution
Development of chimeric dengue virus E glycoproteins with specific amino acid sequences that transfer epitope-specific residues between serotypes to create molecules capable of inducing neutralizing antibodies across all serotypes, including the use of nucleic acid molecules, vectors, and virus-like particles to elicit an immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing dengue vaccines are used, then immunity against some serotypes is achieved, but non-neutralizing antibodies are induced increasing the risk of dengue hemorrhagic fever
Solution Approach 1:
The patent applies local quality by modifying specific regions of the E protein (domains I and II hinge region) while preserving other regions. This targeted modification approach allows the vaccine to present specific epitopes that induce neutralizing antibodies without triggering non-neutralizing responses, thereby improving safety while maintaining protective immunity.
Solution Approach 2:
The chimeric E proteins act as intermediaries between the vaccine platform and the immune system. By designing these chimeric proteins with specific epitope sequences from different serotypes, the patent creates a mediator that guides the immune response toward neutralizing antibodies while avoiding harmful non-neutralizing responses.
2Reliability
If serotype-specific vaccines are developed, then strong neutralizing antibody responses are elicited, but protection against other serotypes is insufficient
Solution Approach 1:
The patent applies universality by designing chimeric E proteins that incorporate epitope sequences from multiple dengue serotypes within a single molecular structure. This allows a single vaccine candidate to potentially induce neutralizing antibodies against multiple serotypes, achieving cross-serotype protection while maintaining strong immune responses.
Solution Approach 2:
The chimeric E proteins are composite structures combining epitope regions from different dengue serotypes. By creating these composite antigens, the patent enables a single vaccine to present multiple serotype-specific epitopes, thereby eliciting broad neutralizing antibody responses against multiple serotypes simultaneously.
3Reliability
If the envelope protein structure is modified to improve immunogenicity, then antibody induction is enhanced, but structural integrity and proper folding may be compromised
Solution Approach 1:
The patent modifies only specific local regions of the E protein (domains I and II hinge region) while preserving the overall protein structure and other critical regions. This localized modification approach enhances immunogenicity by presenting specific epitopes without compromising the global structural integrity and proper folding of the envelope protein.
Data Source
AI summary
The present invention provides compositions and methods of use comprising a chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone, which comprises amino acid substitutions that introduce a dengue virus E glycoprotein epitope from a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone.