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Concomitant delivery of a CTL-restricted peptide antigen and CpG ODN by PLGA microparticles induces cellular immune response

Concomitant delivery of a CTL-restricted peptide antigen and CpG ODN by PLGA microparticles induces cellular immune response

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FISCHER, Stefan, Eva Christine SCHLOSSER, Marc MÜLLER, Noémi CSABA, Hans P. MERKLE, Marcus GROETTRUP, Bruno GANDER, 2009. Concomitant delivery of a CTL-restricted peptide antigen and CpG ODN by PLGA microparticles induces cellular immune response. In: Journal of Drug Targeting. 17(8), pp. 652-661. ISSN 1061-186X. eISSN 1029-2330

@article{Fischer2009Conco-1155, title={Concomitant delivery of a CTL-restricted peptide antigen and CpG ODN by PLGA microparticles induces cellular immune response}, year={2009}, doi={10.1080/10611860903119656}, number={8}, volume={17}, issn={1061-186X}, journal={Journal of Drug Targeting}, pages={652--661}, author={Fischer, Stefan and Schlosser, Eva Christine and Müller, Marc and Csaba, Noémi and Merkle, Hans P. and Groettrup, Marcus and Gander, Bruno} }

Gander, Bruno Poly(lactide-co-glycolide) (PLGA) microparticles (MP) possess immunological adjuvant properties. Yet, exploitation of their full potential has just begun. The purpose of this study was to explore opportunities arising from surface modifications, and attachment and entrapment of combinations of antigen and a Toll-like receptor (TLR) ligand. The cytotoxic T lymphocyte (CTL)-restricted OVA ovalbumin peptide SIINFEKL was microencapsulated into bare, chitosan-coated, and protamine-coated PLGA MP using a microextrusion-assisted solvent extraction process. A TLR-ligand (CpG ODN) was either covalently coupled or physically adsorbed onto the MP surface. The peptide encapsulation efficiency decreased from 71% for uncoated particles to 62% and 45% upon coating with chitosan and protamine, respectively. CpG adsorption efficiency decreased from 93% for protamine-coated particles to 19% and 8% for chitosan and bare particles. Release of the adsorbed CpG was slow and incomplete (23% within 7 days) with the protamine coating, intermediate (>90% within 3 days) with the chitosan coating, and immediate (100% within 3h) without coating. Interestingly, only the uncoated PLGA MP with adsorbed CpG mediated a prominent CTL response in mice at 6 days after immunization, as determined from IFN-; release from antigen-specific CD8+ cells; failure of the other MP formulations was ascribed to the low release of antigen and CpG within the first week after immunization. The study illustrates novel opportunities for PLGA MP vaccines by combining antigens and immunostimulatory ligands. Fischer, Stefan Schlosser, Eva Christine Gander, Bruno eng Müller, Marc Concomitant delivery of a CTL-restricted peptide antigen and CpG ODN by PLGA microparticles induces cellular immune response Groettrup, Marcus Csaba, Noémi 2011-03-23T09:06:31Z Groettrup, Marcus 2011-03-23T09:06:31Z Publ. in: Journal of Drug Targeting 17 (2009), 8, pp. 652-661 Merkle, Hans P. deposit-license Csaba, Noémi Merkle, Hans P. Schlosser, Eva Christine Müller, Marc 2009 Fischer, Stefan

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