Attenuated ASF Virus Vaccine with DIVA Mutation

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Solution Overview

Problem

Current measures for controlling and preventing African Swine Fever (ASF) lack effective treatments and vaccines, leading to significant mortality in domestic pigs and economic losses, with no existing treatment available and limited prevention methods outside of Africa.

Innovation Solution

Development of attenuated African Swine Fever viruses with disrupted EP153R and EP402R gene expression, combined with a Differentiation of Infected from Vaccinated Animals (DIVA) mutation, to create a vaccine that provides protection against wild-type ASFV strains while allowing differentiation between infected and vaccinated animals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current prevention measures (restrictions on incoming pigs and pork products, compulsory boiling of waste animal products, slaughter policy) are implemented, then spread of ASFV can be controlled to some extent, but mortality rate approaches 100% when infection occurs and economic losses are significant

Engineering Contradiction:

Improveprotection against ASFV infectionVSAvoidmortality rate and economic loss

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by developing and administering attenuated ASFV vaccines before infection occurs. The vaccine priming step creates preliminary immunity that protects pigs when challenged with virulent virus, reducing mortality from near 100% to significantly lower levels. This preventive vaccination approach addresses the harmful effects before they can manifest.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses an intermediary approach by employing attenuated virus strains as a mediator between the harmful virulent virus and the immune system. The attenuated virus serves as a safe intermediate that stimulates protective immunity without causing severe disease, thereby reducing mortality and economic losses while maintaining reliability of protection.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If no treatment is available for ASFV infection, then prevention becomes the only option, but prevention methods are limited and mortality remains high when infection occurs

Engineering Contradiction:

Improveavailability of treatmentVSAvoidmortality rate

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent applies inversion by shifting the approach from treating infection after occurrence to preventing infection before it happens. Since no treatment is available for established ASFV infection, the invention inverts the strategy by developing vaccines that prevent infection entirely, thereby addressing the high mortality problem through prevention rather than treatment.

Inventive Principle:

Principle #13The other way round (Inversion)

3Reliability

If conventional vaccination approaches are used, then some protection may be achieved, but differentiation between infected and vaccinated animals cannot be made

Engineering Contradiction:

Improveprotection against infectionVSAvoidability to differentiate infected from vaccinated animals

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent applies the extraction principle by removing specific viral antigens (EP153R and EP402R genes) from the vaccine strain while retaining protective immunity against virulent virus. This selective removal creates a molecular marker that allows serological differentiation between vaccinated and infected animals, as infected animals will produce antibodies against these absent antigens while vaccinated animals will not.

Inventive Principle:

Principle #2Taking out (Extraction)

4Loss of information

If attenuated viruses with disrupted EP153R and EP402R genes are used, then differentiation between infected and vaccinated animals becomes possible, but virus complexity increases

Engineering Contradiction:

Improvedifferentiation capabilityVSAvoidvirus genome structure

Core Design Contradiction:

Loss of informationVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the viral genome into functional segments, specifically targeting and disrupting only the EP153R and EP402R genes while leaving the rest of the genome intact. This selective gene disruption creates the desired differentiation capability with minimal increase in overall virus complexity, as only specific segments are modified rather than the entire genome.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20240293525A1Vaccine against african swine fever virus infection

Publication Date: 2024.09.05 THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

AI summary

The present invention relates to attenuated African Swine Fever viruses. The attenuated viruses protect pigs against subsequent challenge with virulent virus. The present invention also relates to the use of such attenuated viruses to treat and/or prevent African Swine Fever. The invention also relates to EP402R proteins of African Swine Fever virus comprising particular amino acid substitutions, as well as polynucleotides encoding such proteins and African Swine Fever viruses comprising such proteins.