Zika Virus Vaccine Nucleic Acid prM-E Segmentation
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Solution Overview
Problem
Current Zika virus vaccines face challenges in eliciting a protective neutralizing antibody response against both African and Asian lineages, and existing technologies have limitations in immunogenicity and safety, particularly due to inefficient production of prM-E heterodimers.
Innovation Solution
The use of nucleic acid molecules encoding a polyprotein comprising a Zika virus prM protein joined to a Zika virus E protein with a heterologous signal sequence, which directs the expression of virus-like particles (VLPs) capable of inducing an immune response, including the use of modified signal sequences and envelope protein regions from other flaviviruses to enhance immunogenicity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If the entire structural polyprotein region is expressed from cDNA, then the production of prM and E proteins is achieved, but the signal peptidase-mediated cleavage at the amino terminus of prM does not occur efficiently, resulting in deficient secretion of the prM-E heterodimer and lack of immunogenicity
Solution Approach 1:
The patent divides the structural polyprotein region into separate open reading frames (ORFs) for prM and E proteins, rather than expressing them as a single continuous polyprotein. This segmentation allows independent expression and proper signal peptidase-mediated cleavage at the amino terminus of prM, resolving the cleavage inefficiency while maintaining production capability.
Solution Approach 2:
The patent introduces a heterologous signal sequence from a different flavivirus as an intermediary element at the amino terminus of the prM protein. This heterologous signal sequence serves as a mediator that enables efficient signal peptidase recognition and cleavage, which the native Zika virus signal sequence fails to provide when expressed from cDNA.
2Reliability
If Zika virus vaccines are designed to elicit protective neutralizing antibody response, then immunogenicity is improved, but safety limitations arise due to inefficient production of prM-E heterodimers
Solution Approach 1:
By segmenting the structural polyprotein region into separate ORFs, the patent enables proper processing and secretion of prM-E heterodimers, ensuring adequate production of immunogenic material without requiring high-expression constructs that might pose safety risks.
Solution Approach 2:
The patent modifies the genetic construct parameters by using separate ORFs and a heterologous signal sequence, which changes the expression and processing parameters to achieve both high immunogenicity through proper prM-E heterodimer production and safety through efficient secretion that prevents accumulation of potentially harmful intermediates.
Data Source
AI summary
The present invention relates to a vaccine for Zika virus, the vaccine comprising Zika virus membrane and envelope proteins. More specifically, the vaccine comprises nucleic acid molecules encoding modified Zika virus membrane and/or envelope proteins. When introduced into a cell, the encoded proteins are produced, which results in the production of a virus-like particle capable of eliciting an immune response against Zika virus.