Rough Phenotype Salmonella Vector for Avian Adenovirus Vaccine
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Solution Overview
Problem
Current vaccines for Aviadenovirus serogroup 1 (AvA-I) in poultry are ineffective in preventing inclusion body hepatitis, a disease causing up to 50% mortality, due to outdated vaccine technology and lack of licensed commercial vaccines using Salmonella enterica serovar Enteritidis as a vector.
Innovation Solution
Development of an attenuated Salmonella enteritidis strain with a rough phenotype, genetically modified to express AvA-I fiber antigen genes, providing a safe and effective live recombinant vaccine that stimulates a lasting immune response without causing disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional vaccine technology is used for AvA-I, then vaccine development is simple and low-cost, but vaccine effectiveness is poor and cannot prevent inclusion body hepatitis
Solution Approach 1:
The patent uses Salmonella enteritidis as a vector (intermediary) to deliver AvA-I fiber antigen genes to poultry. The Salmonella strain serves as a carrier that transports the viral antigen genes into the host system, enabling effective immune response without requiring direct administration of the virus itself. This mediator approach resolves the contradiction by providing a sophisticated delivery mechanism that overcomes the limitations of traditional vaccines.
Solution Approach 2:
The vaccine combines multiple genetic elements into a composite system: the Salmonella enteritidis bacterial vector is genetically modified to carry and express AvA-I fiber antigen genes. This creates a hybrid vaccine system that integrates bacterial delivery mechanisms with viral antigen expression, achieving both effective delivery and immunogenicity that neither component could achieve alone.
2Reliability
If Salmonella enteritidis is used as a vaccine vector, then vaccine effectiveness and safety are improved, but development complexity and time increase
Solution Approach 1:
The Salmonella enteritidis strain has been pre-modified with multiple deletions (waaL, rfb, wzy, wbbR genes) to create a rough phenotype that is inherently safer and more immunogenic. This preliminary genetic engineering of the vector strain establishes a stable, safe platform before introducing the AvA-I antigen genes, reducing the need for additional safety testing and accelerationating overall development.
Solution Approach 2:
The vaccine development process is segmented into distinct phases: first establishing the safe rough-phenotype Salmonella vector through gene deletions, then separately introducing the AvA-I fiber antigen genes. This segmentation allows parallel optimization of vector safety and antigen effectiveness, reducing total development time compared to simultaneous optimization.
3Reliability
If rough phenotype Salmonella is used, then immune response stimulation is enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent changes the surface phenotype parameter of Salmonella from smooth to rough by deleting specific genes (waaL, rfb, wzy, wbbR). This parameter change enhances immune response effectiveness by making the bacteria more visible to the immune system. The genetic modifications are stable and inherited, so once the rough phenotype strain is established, it maintains this enhanced immunogenicity through standard bacterial culture and propagation methods.
Data Source
AI summary
The present invention relates to a strain of Salmonella enteritidis 3934vac, which has been deleted the waaL gene to obtain a rough phenotype (3934vac DwaaL), the obtaining procedure and the oligos used with the objective of reducing toxicity and maintaining immunogenicity for its application as a vaccine. Another aspect of the present invention relates to a strain of Salmonella enteritidis 3934vac DwaaL, i.e. rough type, which has been modified to express the gene of the avian adenovirus type I fiber, in addition to the procedure for obtaining a Salmonella enteritidis 3034 vac DwaaL strain expressing an AvA-I fiber gene. The invention also comprises the development of a new, live, recombinant, effective and innocuous avian vaccine against the AvA-I virus developed via an insertion and integration process of AvA-I fiber genes in the chromosome of an attenuated and non-pathogenic strain of the bacterium Salmonella enteritidis.