Injectable, Ribbon-Like Microconfetti Biopolymer Platform for Vaccine Applications

Abstract

Previously, high-aspect- ratio ribbon-like microconfetti (MC) composed of acetalated dextran (Ace-DEX) have been shown to form a subcutaneous depot for sustained drug release. In this study, MC were explored as an injectable vaccine platform. Production of MC by electrospinning followed by high-shear homogenization allowed for precise control over MC fabrication. Three distinct sizes of MC, small (0.67 × 10.2 μm2), medium (1.28 × 20.7 μm2), and large (5.67 × 90.2 μm2), were fabricated and loaded with the adjuvant, resiquimod. Steady release rates of resiquimod were observed from MC, indicating their ability to create an immunostimulatory depot in vivo. Resiquimod-loaded MC stimulated inflammatory cytokine production in bone marrow-derived dendritic cells without incurring additional cytotoxicity in vitro. Interestingly, even medium and large MC were able to be internalized by antigen-presenting cells and facilitate antigen presentation when ovalbumin was adsorbed onto their surface. After subcutaneous injection in vivo with adsorbed ovalbumin, blank MC of all sizes were found to stimulate a humoral response. Adjuvant activity of resiquimod was enhanced by loading it into MC and small- and medium-sized MC effectively induced a Th1-skewed immune response. Antigen co-delivered with adjuvant-loaded MC of various sizes illustrates a new potential vaccine platform.

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

“…For example, Ace-DEX, synthesized from 2-ethoxypropene, have been thoroughly investigated. [12][13][14][15][16][17] Compared with Ac-DEX, Ace-DEX has similar physiochemical properties and pH-dependent degradation by hydrolysis. 12 The most significant difference is the degradation products (acetone and ethanol), instead of acetone and methanol as in the case of Ac-DEX.…”

Humoral Response to the Acetalated Dextran M2e Vaccine is Enhanced by Antigen Surface Conjugation

“…Bone marrow-derived dendritic cells (BMDCs) were prepared from BALB/c mice and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), as described previously. , After 9 days of culture in GM-CSF, BMDCs were combined at a 1:1 ratio with DO11.10 hybridoma T-cells and transferred to round-bottomed 96-well plates in supplemented RPMI media (10% inactivated fetal bovine serum (FBS), 100 U/mL penicillin, 100 μg/mL streptomycin, 50 μM 2-mercaptoethanol, 1 × nonessential amino acids, and 2 mM l -glutamine) at 5 × 10 4 (2.5 × 10 4 each of BMDCs and DO11.10s) cells per well. 24 h later, the cys-OVA 323–339 peptide in each of the indicated forms was added to each well, and after 48 h, the cells were centrifuged for 5 min at 500 g , and the supernatants were assessed for IL-2 concentration by ELISA (Invitrogen 88702488).…”

Metal–Organic Coordination Polymer for Delivery of a Subunit Broadly Acting Influenza Vaccine

“…For experiments, the mice received 10 μg of protein (OVA or COBRA HA) and 10 μg of CpG per mouse per dose. These doses of protein and CpG were selected based on what is commonly reported in the literature − and used in our group. ,,, The mice were vaccinated on days 0 and 21, and submandibular blood samples were taken on days 14, 28, and 42. On day 42, the mice were sacrificed and their spleens were removed and processed for antigen recall …”