Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro

Abstract

Biodegradable microspheres (MS) consisting of poly(D,L-lactide-co-glycolide) (PLGA) represent a promising alternative to conventional adjuvants. The adjustable pulsatile release of encapsulated material from such MS offers the potential to mimic the priming and boosting injections of conventional immunization regimens. In this paper, we demonstrate that MS can serve as antigen reservoirs in antigen presenting cells (APC), so that antigen is presented for extended periods of time (up to 9 days). In particular, we could show by measurement of IFN-gamma production that encapsulated peptides were presented to cytotoxic T lymphocytes (CTL) by mouse and human macrophages as well as by human dendritic cells in vitro for a longer time period as compared to soluble peptides. The extended antigen presentation may thus improve the CTL response in vivo. These results may be of paramount importance in cancer vaccination therapy since MS may serve as antigen reservoirs to extend the presentation time by APC used to boost the patient's immune response to tumor antigens.

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

“…[33][34][35] Immunogenicity of recombinant protein Tc24 vaccine with CpG ODN in a PLGA nanoparticle delivery system…”

“…23,27 In particular, production of IFNg is critical for control of T. cruzi infection, unlike IL-4, a T H 2-associated cytokine. 23,[28][29][30] Nanoparticles have been shown to increase antigen uptake by antigen-presenting cells 31 and enhance the T H 1-mediated CD8 C T cell response [32][33][34] through increased MHC I antigen presentation. 35 Nanoparticles can also serve as a depot for antigen, 36 allowing prolonged stimulation of the T H 1 pathway.…”

Preparation and in vitro characterisation of Ehrlichia ruminantium plasmid DNA and proteins encapsulated into and DNA adsorbed onto biodegradable microparticles

“…Adsorption of pDNA onto the PLGA 50:50-COOH cationic microparticles resulted in an increase in diameter of the particles from 1 to 4 m. This is still within the required size range to make them potential targets for APCs. There is an overwhelming number of reports that show that microparticle size plays an important role during transfection with pDNA (Prabha et al, 2002;Scheerlinck and Greenwood, 2008;Heit et al, 2008;Audran et al, 2003). Prabha et al (2002) have shown that smaller nanoparticles (∼70 nm) had a transfection rate 27-fold higher than that of larger nanoparticles (∼97 nm) and therefore a concomitantly higher potential to induce cellmediated immunity.…”

The STEAP1262–270 peptide encapsulated into PLGA microspheres elicits strong cytotoxic T cell immunity in HLA‐A*0201 transgenic mice—A new approach to immunotherapy against prostate carcinoma

“…Stabilization of the HLA-A Ã 0201 peptide complex on the cell surface was compared to the immunodominant, high affinity HLA-A Ã 0201 ligand influenza virus matrix peptide M1 [58][59][60][61][62][63][64][65][66] . Like the M1 reference peptide, PSCA [14][15][16][17][18][19][20][21][22] and PSMA [27][28][29][30][31][32][33][34][35] stabilized HLA-A Ã 0201 even at concentrations below 0.5 mM (Fig. 2).…”

“…Uptake of the antigens and TLR ligands encapsulated in PLGA MS by APCs does not negatively affect their cardinal properties like migratory capacity, cytokine secretion, and antigen presentation [28]. In addition, PLGA MS have beneficial properties like the protection of their content from degradation and the long-lasting depot effect for sustained and prolonged immune responses [29,30]. The addition of potent immune-enhancing adjuvants like cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODN) or polyriboinosinic:polyribocitidylic acid (polyI:C) is necessary for the maturation and crosspriming ability of the APCs.…”