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RESEARCH PRODUCT
PeptoSomes for Vaccination: Combining Antigen and Adjuvant in Polypept(o)ide-Based Polymersomes.
Matthias BrosBenjamin WeberMartin SchererStephan GrabbeCinja KappelMatthias BarzMark Helmsubject
Hydrodynamic radiusPolymers and Plasticsmedicine.medical_treatmentT-LymphocytesDispersityGene ExpressionBioengineeringchemical and pharmacologic phenomenaBone Marrow Cells02 engineering and technology010402 general chemistryLymphocyte Activation01 natural sciencesBiomaterialsPeptoidsDynamic light scatteringAntigenAdjuvants ImmunologicMaterials ChemistrymedicineHumansStatic light scatteringAntigensVaccinesChemistryVesicleVaccinationSarcosineDendritic Cells021001 nanoscience & nanotechnologyMolecular biologyCoculture Techniques0104 chemical sciencesOligodeoxyribonucleotidesPolymersomeB7-1 AntigenCytokinesB7-2 Antigen0210 nano-technologyPeptidesAdjuvantBiomarkersBiotechnologydescription
In this work, the first vaccine is reported based on a PeptoSome, which contains a model antigen (SIINFEKL) and adjuvant (CpG). PeptoSomes are polypept(o)ide-based polymersomes built of a block-copolymer with polysarcosine (PSar) as the hydrophilic block (X n = 111) and poly(benzyl-glutamic acid) (PGlu(OBn)) as the hydrophobic one (X n = 46). The polypept(o)ide is obtained with low dispersity index of 1.32 by controlled ring-opening polymerization. Vesicle formation by dual centrifugation technique allows for loading of vesicles up to 40 mol%. PeptoSomes are characterized by multiangle dynamic light scattering, static light scattering, and cryogenic transmission electron microscopy (cryoTEM). The PeptoSomes have a hydrodynamic radius of 39.2 nm with a low dispersity (µ 2 = 0.1). The ρ-ratio R g /R h of 0.95 already indicates that vesicles are formed, which can be confirmed by cryoTEM. Loaded PeptoSomes deliver the antigen (SIINFEKL) and an adjuvant (CpG) simultaneously into dendritic cells (DCs). Upon cellular uptake, dendritic cells are stimulated and activated, which leads to expression of cluster of differentiation CD80, CD86, and MHCII, but induces excretion of proinflammatory cytokines (e.g., TNFα). Furthermore, DC-mediated antigen-specific T-cell proliferation is achieved, thus underlining the enormous potential of PeptoSomes as a versatile platform for vaccination.
year | journal | country | edition | language |
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2017-11-28 | Macromolecular bioscience |