PRRS Virus N Protein Mutants for Safer Vaccines

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Solution Overview

Problem

Current PRRS vaccines, particularly modified live vaccines, face challenges such as residual virulence, safety concerns, and loss of effectiveness against virulent field strains due to antigenic changes during attenuation, highlighting the need for improved vaccines that provide robust immunity.

Innovation Solution

A genetically modified PRRS virus is developed by mutating or deleting the NLS-2, NoLS, or NES regions of the nucleocapsid protein, resulting in an attenuated virus that retains antigenic characteristics of virulent strains, thereby offering more potent protection and minimizing reversion risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If modified live vaccines are attenuated by serial passage in cell culture, then broader protection against PRRS virus is elicited, but residual virulence and safety concerns arise

Engineering Contradiction:

Improveprotection breadthVSAvoidsafety

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent extracts and removes the virulence factor (nuclear localization signal NLS) from the PRRS virus genome through site-directed mutagenesis. By specifically deleting or mutating the NLS sequence in the nucleocapsid protein gene, the virus is attenuated while retaining its immunogenicity, thus providing broad protection without residual virulence

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the genetic parameter of the virus by introducing specific mutations in the NLS region. This parameter change (mutation of amino acid sequence) fundamentally alters the virus's ability to localize to the nucleus, thereby attenuating virulence while preserving protective immunity

Inventive Principle:

Principle #35Parameter changes

2Reliability

If modified live vaccines are attenuated by serial passage, then virulence is reduced, but antigenic changes cause loss of effectiveness against virulent field strains

Engineering Contradiction:

Improvevirulence reductionVSAvoideffectiveness against field strains

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent selectively removes only the NLS sequence from the virus genome through precise genetic engineering, rather than allowing random antigenic changes to occur during serial passage. This targeted extraction maintains viral antigenicity while ensuring consistent attenuation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces a specific, defined genetic mutation (NLS deletion or substitution) that provides controlled attenuation. This precise parameter change avoids the unpredictable antigenic drift that occurs during traditional serial passage attenuation

Inventive Principle:

Principle #35Parameter changes

3Reliability

If killed vaccines are used, then safety is improved, but robust immunity against heterologous strains is not induced

Engineering Contradiction:

ImprovesafetyVSAvoidimmunity breadth

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses a genetically engineered live virus as an intermediary that carries the attenuating mutation (NLS deletion). This intermediary virus provides the safety of defined attenuation while maintaining the immunogenicity of live virus, inducing robust immunity against heterologous strains without the risks of traditional live vaccine attenuation

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS7544362B1N protein mutants of porcine reproductive and respiratory syndrome virus

Publication Date: 2009.06.09 ZOETIS SERVICES LLC

AI summary

The present invention provides a genetically modified PRRS virus, methods to make it and related polypeptides, polynucleotides and various components. Vaccines comprising the genetically modified virus and polynucleotides are also provided.