LAMP Allergen Constructs for Lysosomal MHC II Targeting
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing LAMP Constructs for treating allergic reactions and allergies have limitations in effectively targeting allergens to the lysosomal/endosomal compartment, leading to variable immune responses and low immunogenicity, and conventional DNA vaccines face challenges in accessing the MHCII presentation pathway without targeting technology.
Innovation Solution
Improved LAMP Constructs comprising specific fragments and variants of LAMP domains that direct allergens to the lysosomal/endosomal compartment for processing and presentation to MHC class II molecules, eliciting a Th1 immune response and generating antibodies, using prime boost protocols and various delivery vehicles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional DNA vaccines are used without targeting technology, then the vaccine can be administered simply, but the allergen cannot effectively access the MHCII presentation pathway resulting in low immunogenicity
Solution Approach 1:
The patent uses LAMP domain fusion proteins as intermediary carriers that mediate the transport of allergen peptides to the MHCII presentation pathway. The LAMP domain acts as a bridge between the allergen and the lysosomal/endosomal compartment, enabling efficient antigen presentation without complex delivery vehicles while maintaining high immunogenicity
2Reliability
If existing LAMP Constructs are used, then some targeting to lysosomal/endosomal compartment is achieved, but the targeting is not effective resulting in variable immune responses
Solution Approach 1:
The patent optimizes specific parameters of the LAMP construct including using the full-length LAMP-1 domain (amino acids 1-382) with specific transmembrane and cytoplasmic regions, controlling the stoichiometry of LAMP:peptide ratios (1:1 to 10:1), and adjusting expression levels to achieve consistent and effective lysosomal targeting that produces reliable immune responses
3Reliability
If full LAMP-1 protein is used in the construct, then complete lysosomal targeting is achieved, but the construct size and complexity increase
Solution Approach 1:
The patent extracts and utilizes only the essential functional domains of LAMP-1 (amino acids 1-382 comprising the lumenal domain, transmembrane region, and cytoplasmic tail) that are necessary for lysosomal targeting, rather than using the complete protein with all non-essential regions, thereby achieving effective targeting with reduced construct complexity
Data Source
AI summary
The present invention provides improved LAMP Constructs comprising specific fragments of the LAMP lumenal domain to deliver allergens to immune cells for enhanced processing. These LAMP Constructs can be used for the treatment of disease and in particular allergic reactions and/or allergies. The improved LAMP Constructs allow for presentation of properly configured three dimensional epitopes for production of an immune response when administered to a subject. The improved LAMP Constructs can be multivalent molecules, and/or can be provided as part of a multivalent vaccine containing two or more LAMP Constructs.