Encapsulation of proteins and peptides into biodegradable poly(d,l-lactide-co-glycolide) microspheres prolongs and enhances antigen presentation by human dendritic cells

Abstract

Dendritic cell (DC)-based immunotherapy has been hampered by the lack of suitable methods for antigen delivery. Here, we use biodegradable poly(D,L-lactide-co-glycolide) microspheres (PLGA-MS) as carriers of peptides and proteins for antigen delivery to human monocyte-derived DC (MoDC). Compared to soluble proteins, MHC classes I and II-restricted presentation of PLGA-MS-encapsulated proteins and peptides by MoDC was markedly prolonged and proteins were presented 50-fold more efficiently on class I molecules. The vaccination of mice with DC loaded with PLGA-MS-encapsulated proteins raised strong and persisting cytotoxic T cell responses. In conclusion, antigen delivery via PLGA-MS markedly enhanced the duration of antigen presentation by human MoDC and the potency of DC-based vaccination.

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

“…Nanocarriers used for delivery of proteins or subunit vaccines enhance antigen uptake by antigen presenting cells and contribute to a prolonged presentation of the vaccine antigen at the cell surface [34,35]. This leads to activation of a cellular immune response, which was exemplified in previous studies showing that PLGA nanoparticleencapsulated antigens, with or without adjuvant, may induce strong T helper type 1 and cytotoxic T cell immune response (Th1/CTL) response when delivered systemically or subcutaneously [15,17,36].…”

“…Journal of Controlled Release 266 (2017) [27][28][29][30][31][32][33][34][35] 3.5. Protective immune response towards recombinant rLM-OVA after intradermal immunization using hollow microneedles CD8 + T cells play an essential role in clearance of the intracellular bacterium Listeria monocytogenes [31].…”

Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease

“…In addition, PLGA MS protect the encapsulated peptides from proteolytic degradation, thus a lower antigen dose is required. Further more, the use of PLGA MS as an antigen delivery device provides a depot effect and therefore a prolonged antigen release [19,35]. This leads to a CTL response that peaks on day 6 and reaches even beyond day 35 after immunization (Fig.…”

Human Plasmacytoid Dendritic Cells Phagocytose, Process, and Present Exogenous Particulate Antigen

“…This is presumably caused by controlled release of encapsulated Ag from the PLGA particle resulting in prolonged and more efficient Ag presentation compared with soluble Ag (21,37). Furthermore, ex vivo Ag loading of moDCs using microparticles is also more efficient than external loading of peptides in MHC molecules.…”

“…Furthermore, ex vivo Ag loading of moDCs using microparticles is also more efficient than external loading of peptides in MHC molecules. Because of the rapid turnover of MHC-peptide complexes on the cell surface, the duration of T cell stimulation in vivo is prolonged on uptake of particulate Ag compared with external loading of peptides (37). Finally, particulate TLR-Ls induced efficient pDC activation comparable to activation induced by soluble TLR-Ls.…”