Consensus HPV E6-E7 DNA Vaccines With Electroporation Delivery
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Solution Overview
Problem
Current HPV vaccines face challenges in immunogenicity when scaled up for larger animals and there is a need for improved vaccines to prevent and treat HPV infections leading to cervical cancer and carcinomas of the lung, tonsil, and larynx.
Innovation Solution
Compositions comprising nucleotide sequences encoding HPV E6-E7 fusion antigens, optimized through codon optimization, RNA optimization, and the addition of immunoglobulin leader sequences, delivered via electroporation to enhance cellular immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional DNA vaccines are used, then safety and stability are improved, but immunogenicity decreases when scaled up for larger animals
Solution Approach 1:
The patent applies codon optimization to modify the nucleotide sequence of the HPV antigens, changing the genetic parameters to enhance protein expression levels. This resolves the contradiction by maintaining the safety of DNA vaccination while improving immunogenicity through optimized codon usage that increases antigen production in larger animals
Solution Approach 2:
The patent creates composite vaccine formulations by combining multiple HPV antigen types (6, 11, 16, 18, 31, 33, 45, 52, 58) into a single DNA vaccine construct. This composite approach maintains the inherent safety of DNA vaccines while achieving broad-spectrum immunogenicity across multiple HPV strains that cause cervical cancer and other malignancies
2Adaptability or versatility
If consensus sequence DNA vaccines are used, then breadth of cellular immune response is improved, but manufacturing complexity increases
Solution Approach 1:
The patent merges multiple HPV E6 and E7 antigen sequences into consensus sequences that represent common epitopes across different HPV strains. This consolidation approach broadens the cellular immune response to cover multiple HPV types while simplifying manufacturing by using a single unified DNA construct rather than separate vaccines for each strain
3Productivity
If electroporation delivery is used, then immunogenicity is improved, but procedure complexity increases
Solution Approach 1:
The patent uses electroporation as an intermediary delivery mechanism that temporarily creates pores in cell membranes to facilitate DNA uptake. This mediator approach significantly enhances immunogenicity by improving antigen presentation while the procedure complexity is managed through standardized electroporation protocols and devices
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 optimized HPV vaccines induce robust and broad cellular immune responses, providing effective prophylaxis and therapy against multiple HPV subtypes, including those associated with cervical cancer and other HPV-related malignancies.
Implementation Method 1
delivered via electroporation to enhance cellular immune responses
Data Source
Figure 1A~1C
Figure 2A~2B
Figure 3A~3B
AI summary
Improved anti-HPV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HPV6 E6E7, HPV11 E6E7, HPV16 E6E7, HPV18 E6E7, HPV31 E6E7, HPV33 E6E7, HPV39 E6E7, HPV45 E6E7, HPV52 E6E7, and HPV58 E6E7. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HPV are disclosed.