Mannose-decorated polymersomes loaded with antigens and TLR7/8 agonists targeting antigen-presenting cells for enhancing vaccine efficacy

Abstract

Directing nanoparticles to specific receptors on antigen-presenting cells (APCs) is a promising strategy for inducing robust immune responses. This approach effectively enhances antigen (Ag) uptake, processing, and presentation, leading to improved Ag-specific immunogenicity. In this study, we introduce a novel method for targeting mannose-binding C-type lectin receptors (mannose receptor, CD206) using mannose-decorated nanoparticles to enhance vaccine efficacy. We developed mannose-decorated polymersomes (Man-PSomes) for co-delivering the model Ag-ovalbumin (OVA) within the inner core and the TLR7/8 dual agonist adjuvant resiquimod (R848) within the bilayer of the hydrophobic membrane. This nanoparticulate vaccine delivery system demonstrated the sustained release of Ag in cellular environments and efficiently facilitated the cellular uptake of Ag and R848 into APCs. Additionally, OVA and R848 co-encapsulated in Man-PSomes (OVA/R848/Man-PSomes) significantly increased the efficiency of APC maturation, cross-presentation, and pro-inflammatory cytokine secretion by T cells in vitro compared to that of soluble OVA/R848 or non-Man-PSomes. OVA/R848/Man-PSomes induced effective Ag-specific antibody production and T cell-mediated cytokine induction in vivo, suggesting that Man-PSomes encapsulating OVA and R848 could serve as potent nanoparticulate vaccine delivery systems that induce cellular and humoral immune responses.