Administration sequence- and formation-dependent vaccination using acid-degradable polymeric nanoparticles with high...

Area of Science:

• Immunology
• Materials Science
• Nanotechnology

Background:

• Vaccines activate the immune system through antigen presentation by antigen-presenting cells (APCs).
• Vaccine carriers can influence antigen processing and presentation, impacting immune responses.

Purpose of the Study:

• To compare two acid-degradable polymeric nanoparticles for encapsulating a model antigen, GFP.
• To evaluate the impact of nanoparticle formulation and vaccination strategy on immune responses.

Main Methods:

• Encapsulation of GFP in ketal-based nanoparticles (KMX/GFP and NKMX/GFP) using electrostatic interactions or molecular affinity.
• In vitro assessment of GFP release kinetics from nanoparticles.
• In vivo vaccination studies in mice to assess humoral immune responses.

Main Results:

• GFP was encapsulated with high efficiency in both nanoparticle formulations.
• NKMX/GFP nanoparticles showed faster GFP release compared to KMX/GFP nanoparticles.
• Repeated injections of nanoparticles alone yielded poorer antibody responses than free antigen.
• Sequential administration of nanoparticles followed by free antigen as prime-boost restored humoral immunity.

Conclusions:

• Polymeric nanoparticle chemistry and vaccination sequencing can modulate immune responses.
• Nanoparticles may primarily aid T cell-mediated antigen presentation, while B cell stimulation requires free antigen.
• Tailored vaccine carrier design and administration schedules are crucial for effective humoral immunity.