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Purified proteins Recombinant proteins Whole inactivated or attenuated organisms

Modern Vaccine Components. Antigens. Purified proteins Recombinant proteins Whole inactivated or attenuated organisms DNA encoded antigens. Immune Potentiators. Delivery Carriers. Oil in water emulsions Aluminum compounds Mineral salts Polymers. Bacterial products Toxins

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Purified proteins Recombinant proteins Whole inactivated or attenuated organisms

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  1. Modern Vaccine Components Antigens • Purified proteins • Recombinant proteins • Whole inactivated or attenuated organisms • DNA encoded antigens Immune Potentiators Delivery Carriers • Oil in water emulsions • Aluminum compounds • Mineral salts • Polymers • Bacterial products • Toxins • Cytokines, peptides

  2. S MOTIVATION A Modular approach to constructing vaccines 100-400 nm Encapsulated antigen subunit Protection during transport Transepithelial cell transport Encapsulated Endosomal disruptor Dendritic Cell recognition Recognition elements Adaptor S Protective transport elements Biodegradable polymer Endosomal Disruption element Antigen

  3. A Sustained release of encapsulated antigen from a biodegradable core. Encapsulated antigen subunit 100-400 nm Biodegradable polymer nanoparticles 50/50 Poly (lactide-co-glycolide) polymer

  4. B High density surface presentation of adaptor elements 100-400 nm Adaptor Proteins

  5. C Long-lived surface presentation Biotin-PE Adaptor Proteins Surface presentation is long-lived with sustained release of antigen

  6. 100-500 nm Antigen-loaded Biodegradable Nanoparticle Polysaccharide Backbone TLR4 Ligand + Lipid A Anchor Antigen-Delivery to Dendritic Cells: Targeting Toll Like Receptor (TL4)

  7. 100-500 nm Antigen-loaded Biodegradable Nanoparticle Polysaccharide Backbone TLR4 Ligand + Lipid A Anchor Antigen-Delivery to Dendritic Cells: Targeting Toll Like Receptor (TL4) Oral Feeding OR LPS/OVA Inject SubQ 7 days Isolate Splenocytes Stimulate on an OVA coated Plate Uncoated/OVA Blank

  8. 100-500 nm Antigen-loaded Biodegradable Nanoparticle Polysaccharide Backbone TLR4 Ligand + Lipid A Anchor Antigen-Delivery to Dendritic Cells: (Subcutaneous Route) Targeting Toll Like Receptor (TL4) Stimulation of Splenocytes from vaccinated mice with OVA antigen 0.5 LPS Particles/OVA 0.45 0.4 0.35 Proliferation Index (Post 3 Days) Unmodified Particles/OVA 0.3 Blank Particles 0.25 0.2 0 50 100 150 OVA (ug/ml)

  9. 100-500 nm Antigen-loaded Biodegradable Nanoparticle Polysaccharide Backbone TLR4 Ligand + Lipid A Anchor Antigen-Delivery to Dendritic Cells: (Oral Route) Targeting Toll Like Receptor (TL4) Oral Vaccination followed by OVA antigen Stimulation of Splenocytes 0.9 0.8 0.7 LPS Particles/OVA 0.6 Proliferation Index (Post 3 Days) 0.5 Unmodified Particles/OVA 0.4 Blank Particles 0.3 0 30 60 90 120 150 OVA (ug/ml)

  10. 0.02 No Elastin (pH= 2) 0.015 Drug released (mg) 0.01 Elastin (pH=2) 0.005 0 0 20 40 60 80 100 Time (hrs) Protection during Transport: Surface modification with pH responsive polypeptides: 200-500 nm pH < 5 37 C Surface modification pH > 5 37 C Elastin (Expanded State) Elastin-Coated nanoparticle pH = 7 pH = 2

  11. PATHFORWARD Transport Optimal Assembly of modular units Recognition of DC subsets Antigen presentation Thanks to: Ira Mellman Mark Saltzman Michael Caplan Robert Samstein Gilbert Addo Stacey Demento Erin Steenblock

  12. D Mediating transport and recognition 100-400 nm Encapsulated antigen subunit Transepithelial cell transport Encapsulated Endosomal disruptor Dendritic Cell recognition Recognition elements Adaptor Biodegradable polymer Endosomal Disruption element Antigen

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