Redox-Responsive Biodegradable Polycation Poly(amido amine) Used As Intranasal Vaccine Delivery Systems

Area of Science:

• Biomaterials Science
• Vaccinology
• Immunology

Background:

• Polycations like polyethylenimine and chitosan are used for mucosal vaccine delivery.
• Biodegradable and environmentally responsive polycations are preferred for better vaccine carriers.
• Redox-sensitive polycations, utilizing disulfide bonds, are ideal for cytoplasmic antigen delivery.

Purpose of the Study:

• To evaluate the potential of a redox-sensitive, biodegradable polycation, poly(amido amine) (PAA), as a mucosal vaccine delivery carrier.
• To assess PAA's ability to complex, encapsulate, and deliver protein antigens.
• To investigate the immunogenicity of PAA-delivered antigens in a preclinical model.

Main Methods:

• Complexation and encapsulation of ovalbumin (model antigen) with PAA.
• Assessment of antigen uptake by dendritic cell line DC2.4.
• Evaluation of antigen residence time and permeation in the nasal cavity.
• Intranasal immunization of Balb/c mice with PAA-delivered H7N9 influenza virus hemagglutinin (HA) antigen.
• Analysis of systemic IgG, mucosal IgA, splenocyte proliferation, cytokine secretion (IFN-γ, IL-4), T cell populations (CD4+, CD8+), and dendritic cell maturation (MHC II).

Main Results:

• PAA effectively complexes and encapsulates protein antigens, enhancing cellular uptake and nasal submucosal permeation.
• PAA/HA formulations induced significantly stronger systemic IgG and mucosal IgA responses compared to controls.
• PAA-delivered HA antigen elicited enhanced splenocyte proliferation, higher levels of IFN-γ and IL-4, increased memory CD4+ and CD8+ T cells, and more mature dendritic cells.
• PAA demonstrated superior induction of cellular immune response compared to previously reported carriers.

Conclusions:

• The redox-responsive polycation PAA is a promising biodegradable carrier for mucosal vaccine delivery.
• PAA significantly enhances both cellular and humoral immune responses, particularly cellular immunity.
• PAA holds potential for the development of efficient mucosal vaccine delivery systems for clinical applications.