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Exponentially Decreasing Antigen Release Reduces Inflammatory Markers in an Antigen-Specific Manner.
Arezoo Esrafili1, Aleksandr Talitckii2, Joshua Kupfer1
1Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, Arizona, USA.
Journal of Biomedical Materials Research. Part A
|July 9, 2025
Summary
Controlled antigen delivery using programmable pumps and biomaterials modulates immune responses. Tailored release kinetics, such as decreasing ovalbumin (OVA) profiles, promote regulatory T-cells (Tregs) and reduce inflammation, enhancing immune regulation and memory.
Area of Science:
- Immunology
- Biomaterials Science
- Vaccine Development
Background:
- Optimizing vaccine efficacy requires innovative strategies to enhance immune responses and reduce the frequency of immunizations.
- Controlled antigen delivery systems are crucial for fine-tuning immune activation and regulation.
- Understanding adaptive immune responses to antigen release kinetics is essential for designing effective vaccines.
Purpose of the Study:
- To investigate the impact of controlled antigen release profiles on immune activation and regulation.
- To compare the effects of exponentially decreasing and increasing ovalbumin (OVA) delivery on adaptive immune responses in mice.
- To identify key immune cell populations and biomarkers associated with distinct immune responses to antigen release kinetics.
Main Methods:
- Utilized programmable infusion pumps and biodegradable PLGA-PEG-PLGA (PPP) depots for controlled OVA delivery in OT-II and wild-type mice.
- Administered OVA via exponentially decreasing and increasing release profiles to mimic infection clearance and induction, respectively.
- Employed Machine Learning (ML) models with Sequential Feature Selection (SFS) to analyze T-cell populations and identify key immune markers.
Main Results:
- Exponentially decreasing OVA delivery promoted regulatory T-cell (Treg) activation and suppressed T-helper type 17 (Th17) responses.
- Exponentially increasing OVA delivery enhanced central memory T-cell (TCM) populations and humoral immune responses.
- Biodegradable PPP depots delivering OVA in a decreasing pattern reduced pro-inflammatory T-helper type 1 (Th1) cells and increased Tregs.
- ML analysis identified specific T-cell markers (e.g., RORγt+, FOXP3+/GATA3+ ratio, CD25+FOXP3+ Tregs) indicative of distinct immune responses to OVA release kinetics.
Conclusions:
- Controlled antigen delivery, particularly via decreasing release profiles, can enhance immune regulation and promote the generation of memory T cells.
- The kinetics of antigen release significantly influences the type and magnitude of adaptive immune responses.
- This study provides novel insights into optimizing vaccine design through precise control over antigen delivery profiles.
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