Polyvalent Filovirus DNA Vaccine Using Consensus Glycoproteins
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Solution Overview
Problem
Current vaccines for filoviruses, such as Marburgvirus, Ebolavirus Sudan, and Ebolavirus Zaire, face challenges in inducing effective immune responses due to high diversity among the viruses, leading to difficulties in developing a universal and broadly-reactive vaccine that provides protection against multiple species, especially given the high lethality rates and potential for outbreaks.
Innovation Solution
A synthetic polyvalent-filovirus DNA vaccine comprising three DNA plasmids encoding the envelope glycoprotein genes of Marburg marburgvirus, Sudan ebolavirus, and Zaire ebolavirus, utilizing a multiagent approach with genetically-optimized sequences and delivery via in vivo electroporation to elicit robust neutralizing antibodies and cytotoxic T lymphocyte responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single-species vaccine is developed for Marburgvirus or Ebolavirus, then effective immune response is induced against that specific virus, but protection against other filovirus species is not achieved due to high viral diversity
Solution Approach 1:
The patent creates a universal vaccine platform that can protect against multiple filovirus species (Marburgvirus and Ebolavirus) through a single vaccine formulation. The vaccine uses conserved epitopes and glycoprotein structures that are common across different filovirus species, enabling one vaccine to provide broad cross-protection rather than requiring separate vaccines for each virus type.
Solution Approach 2:
The patent modifies the vaccine approach by changing the target parameters from virus-specific antigens to conserved epitopes and glycoprotein structures that are shared across filovirus species. By focusing on these conserved parameters rather than variable species-specific parameters, the vaccine achieves broad coverage while maintaining effective immune response.
2Adaptability or versatility
If a universal vaccine is designed to cover multiple filovirus species, then cross-protection is achieved, but the complexity of identifying and targeting conserved epitopes increases
Solution Approach 1:
The patent extracts and isolates the conserved epitopes and glycoprotein structures from the diverse filovirus genomes. By taking out only the conserved elements that are shared across species, the design simplifies the vaccine target rather than attempting to include all viral proteins. This extraction approach reduces complexity while maintaining broad protection.
Solution Approach 2:
The patent focuses on homogeneous, conserved epitopes and glycoprotein structures that are identical or similar across different filovirus species. By targeting these homogeneous elements rather than the heterogeneous species-specific regions, the vaccine design becomes simpler and more straightforward, as the same antigenic targets work for all species.
3Reliability
If existing vaccines are used for filovirus prevention, then some protection is provided, but complete protection against high lethality viruses with 90% mortality rate is not achieved
Solution Approach 1:
The patent employs preliminary action by inducing broad immune responses before exposure to the virus. The vaccine pre-activates the immune system against conserved epitopes and glycoproteins that are common to all filovirus species, so that when infection occurs, the immune system is already primed and ready to respond effectively, preventing the high lethality outcome.
Solution Approach 2:
The patent uses a composite vaccine approach that combines multiple antigenic components (conserved epitopes from different species, glycoprotein structures) into a single vaccine formulation. This composite design creates a synergistic immune response that is stronger and more comprehensive than single-antigen vaccines, achieving complete protection against highly lethal viruses.
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 demonstrates complete protection against MARV and ZEBOV challenges, inducing broad immune responses and neutralizing antibodies, with the ability to be quickly adapted for future outbreak strains, enhancing protection against divergent strains.
Implementation Method 1
A synthetic polyvalent-filovirus DNA vaccine comprising three DNA plasmids encoding the envelope glycoprotein genes of Marburg marburgvirus, Sudan ebolavirus, and Zaire ebolavirus
Implementation Method 2
delivery via in vivo electroporation to elicit robust neutralizing antibodies and cytotoxic T lymphocyte responses
Implementation Method 3
inducing broad immune responses and neutralizing antibodies
Implementation Method 4
inducing broad immune responses and neutralizing antibodies, with the ability to be quickly adapted for future outbreak strains
Data Source
AI summary
Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus filovirus immunogen including a consensus Marburgvirus filovirus glycoprotein MARV GP immunogen, a consensus Ebolavirus Sudan filovirus glycoprotein SEBOV GP immunogen and a consensus Ebolavirus Zaire glycoprotein ZEBOV GP immunogen are disclosed. The coding sequences optionally include operable linked coding sequence that encode a signal peptide. Immunomodulatory methods and methods of inducing an immune response against filovirus, particularly Marburgvirus, Ebolavirus Sudan and Ebolavirus Zaire are disclosed. Method of preventing filovirus infection, particularly infection by Marburgvirus, Ebolavirus Sudan and Ebolavirus Zaire and methods of treating individuals infected with filovirus infection, particularly infection by Marburgvirus, Ebolavirus Sudan and Ebolavirus Zaire are disclosed. Consensus filovirus proteins are disclosed.