Recombinant VSV Vectors Encoding Zika NS1 Protein
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current Zika virus vaccine candidates primarily focus on the prM and E proteins, which may lead to Antibody Dependent Enhancement (ADE) and lack comprehensive protection against Zika virus infection, highlighting the need for alternative immunogenic compositions and methods that induce effective immune responses.
Innovation Solution
Development of recombinant vectors encoding Zika virus nonstructural protein 1 (NS1) and optionally envelope (E) and premembrane (prM) proteins, using a vesicular stomatitis virus (VSV) vector backbone with attenuating mutations, to induce an immune response and provide protection against Zika virus infection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If vaccine candidates focus on prM and E proteins, then immune response is induced, but Antibody Dependent Enhancement (ADE) occurs and comprehensive protection is lacking
Solution Approach 1:
The patent segments the Zika virus antigen into multiple protein components (NS1, E, and prM) that can be independently encoded and expressed. The vector system allows separate expression of these protein subunits, enabling comprehensive immunogenicity while avoiding ADE by controlling the presentation and combination of different antigenic components
Solution Approach 2:
The patent creates a composite immunogenic composition by combining multiple Zika virus protein subunits (NS1, E, and/or prM) within a single vaccine formulation. This composite approach provides comprehensive protection by targeting multiple viral antigens simultaneously, thereby preventing ADE through balanced immune response induction across different protein targets
2Reliability
If recombinant vectors encode multiple Zika virus proteins, then comprehensive immune response is induced, but vector complexity increases
Solution Approach 1:
The patent employs a universal VSV vector backbone that can accommodate and express multiple different Zika virus protein subunits (NS1, E, and/or prM) through standardized genetic construction methods. This multi-functional vector design simplifies the overall system by using a single versatile platform rather than multiple specialized vectors, thereby reducing complexity while maintaining comprehensive immunogenicity
Data Source
AI summary
Embodiments disclosed herein provide compositions, methods, and uses for recombinant vectors encoding Zika virus (ZIKV) protein subunits, and immunogenic compositions thereof. Certain embodiments provide recombinant vectors encoding ZIKV nonstructural protein 1 (NS 1), and optionally, ZIKV envelope (E) protein and premembrane (prM) protein. Other embodiments provide expression cassettes comprising a promoter operably linked to a polynucleotide that encodes the ZIKV NS 1 protein, and optionally ZIKV E and prM proteins. In some embodiments, the disclosed expression cassettes can be incorporated into a vector to produce a recombinant vector. Also provided are immunogenic compositions comprising one or more recombinant vectors described herein, and methods for inducing an immune response against ZIKV in a subject comprising administering to the subject an immunologically effective dose of an immunogenic composition of the present disclosure.