Consensus HEF DNA Vaccine for Influenza D Cross-Lineage Protection
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Solution Overview
Problem
There is a need for an efficacious vaccine to protect against Influenza D virus (IDV) infections in domestic livestock and prevent potential cross-species transmission to humans, as IDV is associated with bovine respiratory disease complex and has a broad host range, including humans, with two co-circulating lineages posing challenges for vaccine development.
Innovation Solution
A DNA vaccine encoding the consensus hemagglutinin-esterase-fusion (HEF) protein of IDV is designed and tested, eliciting high-titer neutralizing antibodies and providing sterilizing protection against IDV infections in a guinea pig model, with the vaccine's sequence showing at least 85-100% homology with the consensus sequences to cover both IDV lineages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a vaccine targeting a specific IDV lineage is developed, then protection against that lineage is achieved, but cross-protection against other lineages is insufficient
Solution Approach 1:
The patent applies universality by designing a consensus HEF vaccine that incorporates amino acid sequences conserved across multiple IDV lineages (D/OK and D/660). This multi-functional vaccine approach allows a single formulation to elicit neutralizing antibodies effective against different IDV lineages, achieving both protection effectiveness and cross-lineage coverage simultaneously
2Reliability
If whole virus vaccines are used, then strong immune response is elicited, but viral genetics can change and reduce vaccine effectiveness
Solution Approach 1:
The patent extracts only the essential protective element from the whole virus - the conserved HEF protein - and uses it as the vaccine antigen. This extraction approach maintains strong immune response generation while eliminating the problem of viral genetic change, as the consensus HEF sequence remains stable across IDV lineages
Solution Approach 2:
The patent changes the vaccine approach from whole virus to subunit protein, fundamentally altering the parameter of vaccine composition. This parameter change allows the vaccine to target conserved molecular features rather than variable viral genomes, ensuring stability and sustained effectiveness
3Reliability
If DNA vaccine encoding consensus HEF is used, then sterilizing protection against multiple lineages is achieved, but vaccine development complexity increases
Solution Approach 1:
The patent applies segmentation by focusing the vaccine on a specific functional segment of the virus - the HEF protein - rather than using the entire virus. This segmentation simplifies the vaccine development process while achieving sterilizing protection, as the HEF segment contains the critical neutralizing epitopes
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The vaccine achieves sterilizing protection against both IDV lineages, reducing viral RNA loads and clinical signs in respiratory tissues, and preventing IDV infection in vaccinated animals, demonstrating its effectiveness in a guinea pig model.
Implementation Method 1
The results showed that the consensus DNA vaccine (SEQ ID NO. 2) elicited high-titer neutralizing antibodies and achieved sterilizing protection against two lineage-representative IDV intra-nasal infections
Implementation Method 2
The vaccine achieves sterilizing protection against both IDV lineages, reducing viral RNA loads and clinical signs in respiratory tissues
Data Source
AI summary
The present disclosure provides a DNA vaccine or immunogenic composition expressing consensus hemagglutinin-esterase-fusion (HEF) protein (FluD-Vax) and a protein-based vaccine utilizing the HEF consensus protein. Methods of making and using the compositions are also provided herein.