Modulating antigen processing through metal-organic frameworks to bias adaptive immunity

Area of Science:

• Nanotechnology in vaccinology
• Immunology and adaptive immunity
• Materials science for drug delivery

Background:

• Nanoparticle vaccines enhance antigen uptake but intracellular processing and release dynamics remain unclear.
• Understanding antigen release is crucial for optimizing vaccine-induced immune responses.
• Metal-organic frameworks (MOFs) offer tunable properties for controlled antigen delivery.

Purpose of the Study:

• To investigate how modulating antigen release rate from MOF nanoparticles affects adaptive immunity.
• To determine the influence of MOF pore size on intracellular antigen processing and T cell responses.
• To explore the potential for personalized vaccine design through controlled antigen release kinetics.

Main Methods:

• Utilized two MOFs (NU-100x series) with differing pore sizes for ovalbumin (OVA) antigen loading.
• Assessed antigen release profiles and intracellular processing influenced by MOF pore size.
• Evaluated downstream CD8+, CD4+ T cell proliferation, cytokine profiles (T_H1/T_H2), and antibody responses (IgG) in vivo.

Main Results:

• Ovalbumin-loaded NU-1003 showed higher CD8+:CD4+ T cell proliferation and T_H1:T_H2 cytokine ratios.
• Ovalbumin-loaded NU-1000 induced stronger antigen-specific IgG responses, including higher long-term antibody production and IgG1:IgG2a ratios.
• SARS-CoV-2 receptor-binding domain (RBD)-loaded NU-1000 demonstrated significantly higher IgG1:IgG2a ratios and broader epitope recognition compared to NU-1003.

Conclusions:

• Antigen release rate, modulated by MOF pore size, critically influences the type and magnitude of vaccine-induced immunity.
• Controlled antigen release can direct adaptive immune responses, favoring either T cell-mediated immunity or antibody production.
• This study provides a framework for engineering nanoparticle vaccines with tunable release profiles for personalized immune strategies.