Self-Cleaving Polyprotein VLP Constructs for Protective Immunity
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Solution Overview
Problem
Current vaccine strategies lack effective compositions capable of inducing protective immunity against target proteins, including infectious agents and target antigens implicated in host pathologies, such as viruses and cancer-associated antigens.
Innovation Solution
A vaccine construct comprising a nucleic acid sequence encoding a polyprotein with immunogen and two or more viral structural proteins separated by a signal peptidase sequence, allowing self-assembly into virus-like particles (VLP) through host cell peptidase-dependent cleavage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccine strategies using live attenuated organisms, killed or inactivated organisms, or subunit vaccines are used, then vaccine production is achievable, but the ability to induce protective immunity against target proteins including infectious agents and cancer-associated antigens is insufficient
Solution Approach 1:
The polyprotein is segmented into multiple functional domains: an immunogen domain and multiple viral structural protein domains separated by signal peptidase sequences. This segmentation allows the viral structural proteins to be cleaved and self-assembled into VLPs while the immunogen remains integrated, enabling both structural integrity and immunogenicity in a single construct.
Solution Approach 2:
The invention merges the immunogen with viral structural proteins in a single polyprotein construct. The immunogen is fused to multiple viral structural protein coding sequences separated by signal peptidase sites, creating a unified molecular entity that simultaneously provides immunogenicity and forms functional VLP structures.
2Productivity
If the polyprotein is expressed in a host cell, then the signal peptidase sequence undergoes peptidase-dependent cleavage to liberate viral structural proteins, but the complexity of the expression and cleavage process increases
Solution Approach 1:
The signal peptidase sequences are designed to be recognized and cleaved by host cell peptidases that are naturally present in the expression system. This self-service mechanism utilizes the host cell's own enzymatic machinery to perform the cleavage, eliminating the need for external protease treatment or complex purification steps while maintaining high productivity.
3Reliability
If the liberated structural proteins self-assemble into VLP, then the vaccine construct achieves functional integrity, but the precision of self-assembly control becomes more difficult to manage
Solution Approach 1:
The invention utilizes changes in cellular conditions during expression and processing to control self-assembly. The signal peptidase cleavage and subsequent VLP self-assembly are triggered by specific cellular parameters such as protein folding, chaperone availability, and post-translational modification conditions, enabling precise control over the assembly process without requiring external intervention.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution enables the production of VLPs that effectively induce immune responses, providing a platform for delivering immunogens and generating protective immunity against various pathogens, including viruses and cancer antigens.
Implementation Method 1
the signal peptidase sequence undergoes host cell peptidase-dependent cleavage to liberate the two or more viral structural proteins
Implementation Method 2
allowing the liberated structural proteins to self-assemble into a VLP
Data Source
AI summary
Disclosed herein are vaccine constructs for producing a virus-like particle (VLP) capable of raising an immune response to an immunogen, and uses thereof, wherein the constructs comprise nucleic acid sequences encoding an immunogen and a polyprotein, wherein the polyprotein comprises two or more viral structural proteins, wherein at least two of the two or more viral structural proteins are separated by a signal peptidase sequence such that, when the polyprotein is expressed in a host cell, the signal peptidase sequence undergoes host cell peptidase-dependent cleavage to liberate the two or more viral structural proteins, thereby allowing the liberated structural proteins to self-assemble into a VLP carrying the immunogen.