Deoptimized LT/F Vector Vaccines Suppress Avian Virus Shedding
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Solution Overview
Problem
Current vaccines for infectious laryngotracheitis in chickens are either unsafe due to rapid reversion to virulence or insufficient in inducing a strong immune response, and vectored vaccines do not effectively suppress virus shedding.
Innovation Solution
Development of a deoptimized recombinant laryngotracheitis virus vector (rLT/F) carrying fusion genes of avian viruses like Newcastle disease virus (NDV) to induce a robust immune response, using codon pair bias deoptimization and gene editing technologies, administered via various routes including gel administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chicken embryo origin (CEO) vaccines are used, then robust immunity is stimulated which suppresses shedding of field virus, but the vaccine can revert to virulence quickly and is associated with mild disease
Solution Approach 1:
The patent divides the vaccine system into two separate components: a safe vectored vaccine for routine administration and a CEO-derived component for outbreak control. This segmentation allows each component to fulfill its specific function without the drawbacks of the other - the vectored vaccine provides safety while the CEO component provides strong immunity suppression when needed.
Solution Approach 2:
The patent introduces a vectored vaccine as an intermediary solution that bridges the gap between safety and efficacy. This intermediary vaccine provides a safe platform for routine use while maintaining the capability to induce protective immunity, thereby mediating between the safety requirements and the need for virus shedding suppression.
2Object-affected harmful factors
If tissue culture origin (TCO) vaccines are used, then safety is improved, but the immune response is insufficient for controlling outbreaks
Solution Approach 1:
The patent creates a dynamic vaccination strategy where the choice of vaccine type changes based on the situation. The vectored vaccine (safe but milder) is used for routine prophylaxis, while CEO-derived vaccines (stronger but riskier) are reserved for outbreak control. This dynamic approach optimizes both safety and efficacy at different times.
Solution Approach 2:
The patent changes the parameters of vaccine selection based on the epidemiological context. By adjusting which vaccine type is deployed (vectored vs. CEO-derived) depending on whether it's routine vaccination or outbreak response, the system optimizes the balance between safety and immune response strength.
3Object-affected harmful factors
If vectored vaccines are used, then safety is improved, but full immunity is not developed quickly and virus shedding is not suppressed
Solution Approach 1:
The patent segments the vaccination program into routine prophylaxis (using safe vectored vaccines) and outbreak response (using faster-acting CEO-derived vaccines). This segmentation allows the vectored vaccine to provide safe, gradual immunity building during normal conditions while reserving faster options for emergencies.
Solution Approach 2:
The patent implements preliminary vaccination with safe vectored vaccines to build baseline immunity, then has the capability to administer booster doses or switch to CEO-derived vaccines when outbreaks occur. This preliminary action ensures safety is maintained while preparing the system for faster response when needed.
Data Source
AI summary
The present invention provides compositions and methods for immunizing a subject in need thereof again an avian pathogen. In one aspect, the invention provides a composition for immunizing an avian subject against a pathogen comprising: a) a recombinant laryngotracheitis virus vector (rLT); and b) a fusion gene of an avian virus (F) inserted into the recombinant laryngotracheitis virus vector (rLT/F); wherein the recombinant laryngotracheitis virus vector inserted with the fusion gene of the avian virus (rLT/F) is deoptimized to generate deoptimized rLT/F vaccine candidates; and wherein the deoptimized rLT/F vaccine candidates are administered to the subject in need thereof.


