moDC-Targeted Mucosal Vaccine Composition for Lung Antibody Response
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There are few mucosal vaccines approved due to challenges in developing safe and effective mucosal adjuvants, limiting the effectiveness of mucosal vaccination against mucosal pathogens.
Innovation Solution
A vaccine composition comprising an antigen, a cyclic dinucleotide (CDN), soluble tumor necrosis factor (TNF), and a CD64 antibody or antibody fragment, which activates monocyte-derived dendritic cells (moDCs) to induce lung mucosal antibody responses, leveraging a new subset of dendritic cells with unique markers TNFR2−pRelB PD-L1− CX3CR1+ cDC2.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mucosal vaccines are administered to induce protective immunity against mucosal pathogens, then vaccine efficacy is improved, but the lack of safe and effective mucosal adjuvants limits their approval and widespread use
Solution Approach 1:
The patent uses a targeted adjuvant system consisting of an anti-CD64 antibody conjugated to TNF-alpha as an intermediary to specifically activate moDCs at the mucosal site. This targeted approach overcomes the limitation of non-specific mucosal adjuvants by delivering the immune-stimulating effect precisely to the desired cell type (moDCs) through the CD64 receptor, thereby improving reliability while maintaining ease of manufacture
Solution Approach 2:
The patent changes the parameter of adjuvant specificity by using the anti-CD64 antibody to target a specific receptor on moDCs. This parameter change from non-specific to specific targeting enables the adjuvant to effectively activate the desired immune cells without affecting other cell types, thus improving vaccine efficacy while keeping the formulation manageable
2Ease of operation
If conventional mucosal adjuvants are used, then administration is simple, but they fail to generate effective mucosal antibody responses
Solution Approach 1:
The anti-CD64 antibody-TNF-alpha conjugate acts as a targeted intermediary that bridges the adjuvant effect to specific moDCs through the CD64 receptor. This maintains the simplicity of mucosal administration while dramatically improving the reliability of generating mucosal antibody responses by ensuring the adjuvant signal reaches the correct immune cells
Solution Approach 2:
The patent segments the immune response by specifically targeting moDCs (monocyte-derived dendritic cells) rather than attempting to activate all immune cells. The anti-CD64 antibody provides specificity for moDCs, which then orchestrate the mucosal antibody response, achieving reliable results through focused cellular targeting while maintaining simple administration
Data Source
AI summary
Described herein are novel vaccine compositions and methods for use thereof in inducing an immune response in a subject especially aged subjects. Specifically exemplified are vaccine compositions that include an antigen; a cyclic dinucleotide; soluble tumor necrosis factor (TNF); or a CD64 antibody or antibody fragment. Optionally, the vaccine composition comprises a TNF conjugated with a moDC targeting moiety in addition to or in place of TNF or CD64 antibody or antibody fragment, or both TNF and CD64 antibody or antibody fragment.