Polyvalent Attenuated Fish Vaccine Without Marker Genes
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Solution Overview
Problem
Current aquaculture practices face challenges in effectively preventing and treating diseases in fish due to the limitations of chemical antibiotics, including environmental pollution, drug-resistant pathogens, and the inconvenience and inefficacy of existing vaccines, particularly for Vibrio anguillarum and V. alginolyticus infections, which are prevalent in Chinese aquaculture.
Innovation Solution
Development of a polyvalent live, attenuated bacterial vaccine without marker genes, specifically targeting Vibrio species, using deletion mutant strains of Vibrio anguillarum that repress synthesis of aromatic amino acids, folic acid, and virulence factors like siderophore anguibactin, ensuring safe and economic prophylaxis and treatment through convenient administration methods like immersion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical antibiotics are used to control and prevent fish diseases, then disease control effectiveness is improved, but environmental pollution and drug-resistant pathogen occurrence worsen
Solution Approach 1:
The patent changes the fundamental parameter of disease control from chemical antibiotics to biological vaccines, specifically using live attenuated bacteria with deleted virulence genes. This parameter change eliminates the harmful effects of antibiotic resistance and environmental pollution while maintaining disease protection through immunization mechanisms
Solution Approach 2:
The patent extracts and removes the harmful virulence factors (such as siderophore synthesis genes like angE and aromatic amino acid synthesis genes like aroC) from the Vibrio bacteria while retaining the immunogenic components. This creates an attenuated strain that can stimulate immunity without causing disease or producing harmful substances
2Reliability
If kill vaccine is used for fish vaccination, then prophylaxis effect is improved, but administration convenience and treatment efficacy worsen
Solution Approach 1:
The patent changes the vaccine form parameter from inactivated (kill) vaccine to live attenuated vaccine. This parameter change enables the vaccine to be administered through immersion methods rather than injection, greatly improving ease of operation while maintaining strong immunogenicity and prophylaxis effects
Solution Approach 2:
The live attenuated vaccine strains can be absorbed and processed by the fish through immersion, allowing the fish to self-vaccinate without requiring injection procedures. The attenuated bacteria colonize the fish gut and provide ongoing immune stimulation
3Ease of operation
If traditional attenuated live vaccine with marker genes is used, then convenient administration is improved, but environmental safety and product safety worsen due to antibiotic resistance genes
Solution Approach 1:
The patent removes the harmful marker genes (such as antibiotic resistance genes like cat and tet) from the attenuated vaccine strain construction process. The virulence attenuation is achieved through deletion of specific virulence factors (siderophore synthesis genes, aromatic amino acid synthesis genes) without requiring antibiotic resistance markers, thereby eliminating the risk of antibiotic resistance gene transfer to environmental bacteria
Solution Approach 2:
The patent changes the genetic modification strategy from using antibiotic resistance markers to using virulence factor deletion for strain attenuation. This parameter change in the construction approach eliminates antibiotic resistance genes while maintaining the convenience of live attenuated vaccine administration
4Ease of manufacture
If monovalent vaccine is used, then vaccine development simplicity is improved, but protection scope against multiple Vibrio species worsens
Solution Approach 1:
The patent creates a polyvalent vaccine platform using attenuated Vibrio anguillarum strains that can provide cross-protection against multiple Vibrio species (V. anguillarum, V. alginolyticus, V. parahaemolyticus). The attenuated strain serves multiple functions: it is safe due to virulence gene deletion, highly immunogenic as a live vaccine, and provides broad spectrum protection through shared antigenic components across Vibrio species
Data Source
AI summary
A novel polyvalent attenuated live bacterial vaccine for preventing and curing vibriosis of cultivated fish is provided. The vaccine mainly comprises attenuated deletion strain of Vibrio anguillarum without marker gene, which has significant low toxicity, but remains immunogenicity against wild type strain of V. anguillarum, as compared with wild type strain MVM425. Moreover, the vaccine strain has excellent cross immunoprotection against Vibrio alginolyticus. The attenuated live vaccine made from the vaccine strain is effective to prevent and cure vibriosis of fish resulted from wild type strain of V. anguillarum and V. alginolyticus.