Linking Adjuvant Immune Stimulation to Spatiotemporal Dynamics via Cross-Scale Photoacoustic Microscopy

Area of Science:

• Immunology
• Biomedical Imaging
• Materials Science

Background:

• Adjuvants stimulate the innate immune system, crucial for vaccine efficacy.
• Understanding adjuvant spatiotemporal distribution is key to correlating it with immune activation.
• Current methods lack the cross-scale resolution to track adjuvants dynamically.

Purpose of the Study:

• To develop and utilize a cross-scale photoacoustic/fluorescence dual-modality imaging system.
• To dynamically track adjuvant distribution from the cellular to the organismal level.
• To correlate adjuvant spatiotemporal dynamics with immune activation and decipher causal mechanisms.

Main Methods:

• Development of a cross-scale photoacoustic/fluorescence dual-modality imaging system.
• Single-cell imaging to assess macrophage activation post-adjuvant uptake.
• High-resolution photoacoustic microscopy (PAM) for intravascular kinetics in zebrafish.
• Fluorescence microscopy in an inflammation model to quantify immune cell recruitment.

Main Results:

• Macrophages showed differential activation based on adjuvant type.
• PAM revealed size-dependent intravascular kinetics, accumulation, and clearance of adjuvants.
• CpG oligodeoxynucleotides, nano/micron aluminum adjuvants enhanced immune cell recruitment by 5-fold, 2-fold, and 1.5-fold, respectively.
• The imaging system quantitatively linked immune outcomes to adjuvant spatiotemporal dynamics.

Conclusions:

• Adjuvant-induced immune activation results from synergistic interactions between chemical composition and spatiotemporal distribution.
• The study deciphers a causal mechanism by bridging single-cell behavior with systemic biodistribution.
• This imaging-driven framework provides quantitative design principles for precision vaccine adjuvants.