Modified Live PRRS Vaccine Strain Attenuation
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Solution Overview
Problem
Current PRRS vaccines lack sufficient safety and efficacy in protecting against heterologous virus challenges, with modified live virus vaccines showing reversion to virulence and limited effectiveness against diverse wild-type strains, while inactivated vaccines have safety advantages but limited efficacy.
Innovation Solution
Development of a modified, live PRRS vaccine virus strain with a consensus complementary DNA sequence at least 90% identical to specific sequences, passaged extensively in tissue culture cells to ensure attenuation and low probability of virulence reversion, combined with an immunogenic composition including a pharmaceutically acceptable excipient or adjuvant for enhanced immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If modified live virus vaccines are used to provide protection against PRRS virus, then immunity against challenge is generated, but the vaccine virus may revert to virulence and cause disease in vaccinated animals
Solution Approach 1:
The vaccine virus is segmented into multiple distinct viral strains (e.g., strains from different phylogenetic groups) that are combined in a single vaccine composition. This segmentation allows the vaccine to provide broad protective immunity against diverse PRRS virus challenges while each individual strain remains attenuated, reducing the risk of reversion to virulence
Solution Approach 2:
The vaccine composition is a composite formulation containing multiple attenuated PRRS virus strains with different genetic backgrounds and phylogenetic origins. This composite approach combines the advantages of different strains to achieve broad-spectrum protection while maintaining safety through the attenuated nature of each component strain
2Reliability
If modified live virus vaccines are used to provide protection against PRRS virus, then immunity is generated, but effectiveness against heterologous virus challenges is limited
Solution Approach 1:
The vaccine composition is designed with multi-functionality to protect against multiple different PRRS virus strains simultaneously. By incorporating several attenuated strains representing different phylogenetic groups and geographic origins, the single vaccine formulation achieves universal protection against heterologous virus challenges that would not be possible with a single-strain vaccine
Solution Approach 2:
The vaccine employs parameter changes by selecting virus strains with specific genetic characteristics, phylogenetic backgrounds, and attenuation levels. By carefully choosing strains with complementary properties (e.g., different ORF5 sequences, different passage histories), the vaccine achieves broad adaptability against heterologous challenges while maintaining controlled attenuation
3Object-affected harmful factors
If inactivated vaccines are used to ensure safety, then safety profile is improved, but efficacy against heterologous challenge is limited
Solution Approach 1:
The vaccine uses parameter changes by transitioning from inactivated (killed) virus to live attenuated virus, while carefully controlling the attenuation parameters through extensive tissue culture passage. This allows the vaccine to maintain safety through controlled attenuation while significantly improving efficacy by allowing the virus to replicate and induce a more robust and broader immune response against heterologous challenges
Data Source
AI summary
The present invention relates to modified, live Porcine Reproductive and Respiratory Syndrome viruses. Viruses were genetically analyzed and selected based on phylogenetic grouping for modification by repeated passage in tissue culture. The modified, live viruses were assessed for the ability to provide protective immunity to heterologous viruses. The modified, live viruses are useful in vaccines, particularly in vaccines which can treat infection of swine by multiple heterologous viruses.