HPV E6 E7 T Cell Epitopes for Cervical Malignancy Vaccines
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current understanding of tumor-infiltrating lymphocytes in HPV-associated malignancies, particularly for high-risk subtypes like HPV16, 18, 31, 33, and 45, is limited, hindering the development of effective prevention, therapy, and diagnosis strategies.
Innovation Solution
Identification of novel CD4+ and CD8+ T cell epitopes specific to HPV16 and HPV18, which are targets for tumor-infiltrating lymphocytes, utilizing synthetic peptides that induce a robust immune response and are optimized for use in vaccines to enhance prevention and therapy of HPV-related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional vaccine approaches targeting only a few HPV epitopes are used, then vaccine development is simpler, but the immune response coverage is insufficient and does not target all relevant E6 and E7 oncoprotein regions
Solution Approach 1:
The E6 and E7 oncoproteins are divided into multiple overlapping peptide segments (e.g., E6 peptides 1-20, 21-40, 41-60, 61-80, 81-100 and E7 peptides 1-20, 21-40, 41-60, 61-80, 81-100). Each peptide segment is designed to be recognized by specific T cell epitopes, ensuring comprehensive coverage of the entire oncoprotein sequence. This segmentation allows the vaccine to target multiple regions simultaneously while maintaining manageable individual peptide components.
Solution Approach 2:
The vaccine composition is designed to serve multiple functions simultaneously: it provides broad epitope coverage across different HPV types (16, 18, 31, 33, 45), stimulates both CD4+ and CD8+ T cell responses, and targets multiple oncoprotein regions. The multi-peptide formulation achieves universal protection against various high-risk HPV subtypes while maintaining a unified vaccine structure.
2Measurement precision
If T cell cultures are established from cervical tumor tissue to identify HPV-specific epitopes, then accurate identification of tumor-infiltrating lymphocyte targets is achieved, but the process is technically difficult and time-consuming
Solution Approach 1:
The patent performs preliminary identification of HPV-specific T cell epitopes from tumor-infiltrating lymphocytes before vaccine formulation. By first isolating and characterizing the epitopes recognized by TILs (using techniques like peptide pools and ELISPOT assays), the researchers establish a precise target list. This preliminary epitope mapping guides the subsequent design of the multi-peptide vaccine, ensuring that only the most relevant and immunogenic epitopes are included in the final formulation.
3Duration of action of moving object
If a limited number of HPV epitopes are targeted in the vaccine, then the vaccine formulation is simpler, but the immune response is not prolonged or enhanced sufficiently
Solution Approach 1:
The multi-peptide vaccine formulation ensures continuous immune stimulation by targeting multiple epitopes across different time points and cell types. As some epitopes may be recognized earlier by certain T cell populations while others are recognized later or by different cell types, the combined peptide formulation maintains sustained immune activation. This continuous useful action results in prolonged immune response duration compared to single-epitope vaccines.
Data Source
AI summary
The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B.