PRRSV Recombinant Antigen Composition for M1 and Th1 Activation
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Solution Overview
Problem
Current PRRSV vaccines, including live-attenuated, inactive, subunit, and nucleic acid vaccines, fail to provide adequate protection against heterologous viruses and face challenges in inducing effective immune responses due to the virus's ability to evade the host immune system.
Innovation Solution
A recombinant antigen composed of PRRSV dual structural proteins and T-cell epitopes, expressed in an eukaryotic system, promotes pro-inflammatory M1-phenotype polarization of porcine alveolar macrophages and activates Th1 immune responses, reducing receptor CD163 expression for viral entry.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live-attenuated vaccines are used, then cellular and humoral immune responses are induced simultaneously, but neutralizing antibody titers are low providing less protection against heterologous viruses and risks of virus shedding and reverting to virulent form
Solution Approach 1:
The patent extracts only the essential immunogenic components (structural proteins ORF5 and ORF6) from the complete virus, creating a subunit vaccine that eliminates the risks associated with live virus while preserving the ability to induce immune responses. This extraction approach removes the harmful elements (virulence factors) while retaining the protective antigens.
Solution Approach 2:
The patent combines multiple viral proteins (ORF5 and ORF6 structural proteins with T-cell epitopes) into a composite antigen formulation. This composite approach enhances both humoral and cellular immune responses simultaneously, overcoming the limitation of live-attenuated vaccines that produce weak neutralizing antibodies while maintaining safety.
2Object-affected harmful factors
If inactive virus vaccines are used, then safety is improved without risk of reversion, but only humoral immune response is induced requiring twice vaccination and providing no protection against heterologous viruses
Solution Approach 1:
The patent creates a composite antigen containing both B-cell epitopes (for humoral response) and T-cell epitopes (for cellular response) within the ORF5 and ORF6 protein structure. This dual-epitope design enables simultaneous induction of both humoral and cellular immune responses in a single vaccination, eliminating the need for booster shots while maintaining safety.
Solution Approach 2:
The patent designs the recombinant antigen to possess multiple functions: it serves as both a humoral antigen (inducing neutralizing antibodies) and a T-cell antigen (inducing cellular immunity). This multi-functionality allows a single vaccine formulation to provide comprehensive protection against heterologous viruses while maintaining safety, unlike traditional inactivated vaccines.
3Object-affected harmful factors
If subunit vaccines focusing on ORF5 are used, then safety and heterologous virus protection are improved, but PRRSV evades immune system through diverse mechanisms causing development difficulties
Solution Approach 1:
The patent combines ORF5 and ORF6 structural proteins into a single recombinant antigen formulation. ORF5 provides strong B-cell epitopes for humoral immunity, while ORF6 contributes T-cell epitopes for cellular immunity. This composite approach creates a more comprehensive immune response that can better counteract viral evasion mechanisms while maintaining manageable development complexity.
Solution Approach 2:
The patent segments the viral immunogenic components into distinct functional elements (ORF5 structural protein for humoral response, ORF6 structural protein for cellular response) and reassembles them in an optimized configuration. This segmentation allows for targeted enhancement of specific immune responses while simplifying the overall vaccine design and production process.
Data Source
AI summary
The present invention relates to a recombinant antigen and an isolated polynucleotide of porcine reproductive and respiratory syndrome virus (PRRSV), a composition including the same and a method of making the same. The recombinant antigen is a chimeric protein of PRRSV dual structural proteins and T-cell epitope. The polynucleotide encodes an amino acid sequence of the recombinant antigen. The recombinant protein expressed by the polynucleotide in an eukaryotic expression system can be beneficial for mass production and purification. An immunogenic composition including the recombinant antigen can promote pro-inflammatory M1-phenotype polarization of porcine alveolar macrophages (PAMs), reduce receptor CD163 expression that is mediated for viral entry and activate T helper (Th1) immune responses, thereby being applied to a vaccine composition against PRRSV.