Immunogenic Peptides Suppress Viral Vector Immune Responses
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Solution Overview
Problem
The host immune response towards viral vector proteins, particularly from adenoviruses used in gene therapy and gene vaccination, leads to inflammation and cytotoxicity, limiting the effectiveness of these treatments due to pre-existing immune responses and the high immunogenicity of adenoviruses, which triggers both innate and adaptive immune reactions.
Innovation Solution
The use of isolated immunogenic peptides that include a T-cell epitope from viral vector proteins combined with a redox motif, such as C-(X)2-[CST] or [CST]-(X)2-C, to prevent or suppress immune responses by inducing CD4+ regulatory T cells that are cytotoxic to cells presenting viral vector proteins, thereby reducing activation of CD4+ and CD8+ effector T cells and inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors are used for gene therapy and gene vaccination, then transgene expression and antigen delivery are achieved, but immune responses lead to inflammation and cell lysis, aborting transgene expression
Solution Approach 1:
The patent applies preliminary anti-action by pre-administering immunogenic peptides containing T-cell epitopes from viral vector proteins before gene therapy or gene vaccination. This pre-exposure induces regulatory T cells that suppress the harmful immune response to viral vectors, preventing inflammation and cell lysis that would otherwise abort transgene expression. The peptides are given prophylactically to establish immune tolerance before the therapeutic viral vector is introduced.
Solution Approach 2:
The patent uses immunogenic peptides as intermediaries between the host immune system and the therapeutic viral vector. These peptides contain specific T-cell epitopes that act as mediators to induce regulatory T cells, which then modulate the immune response to the viral vector. The peptides serve as a bridge to establish immune tolerance without requiring direct modification of the viral vector itself.
2Productivity
If adenovirus vectors are used, then high transduction efficiency is achieved, but high immunogenicity triggers acute innate immune response and adaptive response, causing cytotoxicity
Solution Approach 1:
The patent extracts the immunogenic T-cell epitopes from the adenovirus vector proteins and uses them as separate immunogenic peptides for pre-exposure. By taking out these specific epitopic regions and using them independently, the patent enables targeted induction of regulatory T cells against the most immunogenic parts of the vector without compromising the transduction efficiency of the full viral vector. This separation allows the therapeutic vector to maintain its function while the extracted epitopes serve to modulate the immune response.
3Reliability
If pre-existing immune response towards viral vector proteins is present, then immune tolerance should be beneficial, but detrimental results occur on vaccination outcome
Solution Approach 1:
The patent changes the quality parameter of the pre-existing immune response by using specific immunogenic peptides containing T-cell epitopes that preferentially induce regulatory T cells rather than effector T cells. By carefully selecting and designing peptides with specific epitopic sequences, the patent transforms the nature of the pre-existing immunity from potentially harmful effector responses to beneficial regulatory responses that suppress harmful immunity while preserving vaccination efficacy.
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
This approach effectively prevents or suppresses immune responses to viral vectors, allowing for sustained transgene expression by inducing tolerance to viral vector proteins, thus overcoming a major obstacle in gene therapy and gene vaccination by eliminating antigen-presenting cells presenting MHC class II-bound peptides from viral vector proteins.
Implementation Method 1
immunogenic peptides comprising an MHC Class II restricted T-cell epitope from a viral vector protein and, immediately adjacent to said T-cell epitope or separated from said T-cell epitope by a linker of up to 7 amino acids, a C-(X)2-[CST] or [CST]-(X)2-C redox motif
Data Source
Figure 1
AI summary
The present invention relates to the use of immunogenic peptides comprising a T-cell epitope derived from a viral vector antigen and a redox motif such as C- (X)2-[CST] or [CST]-(X)2-C in the prevention and/or suppression of immune responses to viral vectors and in the manufacture of medicaments therefore.