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Modern Vaccine Components
Antigens
•Purified proteins
•Recombinant proteins
•Whole inactivated or
attenuated organisms
• DNA encoded antigens
Immune Potentiators
Delivery Carriers
•Bacterial products
•Oil in water emulsions
•Toxins
•Aluminum compounds
•Cytokines, peptides
•Mineral salts
•Polymers
MOTIVATION
A Modular approach to constructing vaccines
100-400 nm
Encapsulated
antigen
subunit
Protection during
transport
Transepithelial
cell transport
Dendritic Cell
recognition
Encapsulated
Endosomal
disruptor
S
S
Recognition
elements
Adaptor
Protective transport
elements
Biodegradable polymer
Endosomal Disruption
element
Antigen
A Sustained release of encapsulated antigen from a
biodegradable core.
100-400 nm
Biodegradable polymer nanoparticles
Encapsulated
antigen
subunit
50/50 Poly (lactide-coglycolide) polymer
B High density surface presentation of adaptor elements
100-400 nm
Adaptor
Proteins
C Long-lived surface presentation
Biotin-PE
Adaptor
Proteins
Surface presentation is long-lived with
sustained release of antigen
Antigen-Delivery to Dendritic Cells:
Targeting Toll Like Receptor (TL4)
Polysaccharide Backbone
TLR4 Ligand
100-500 nm
Antigen-loaded
Biodegradable Nanoparticle
+
Lipid A Anchor
Antigen-Delivery to Dendritic Cells:
Targeting Toll Like Receptor (TL4)
Polysaccharide Backbone
TLR4 Ligand
100-500 nm
Antigen-loaded
Biodegradable Nanoparticle
+
Lipid A Anchor
Oral
Feeding
LPS/OVA
Inject
SubQ
Uncoated/OVA
Blank
7 days
Isolate
Splenocytes
Stimulate on an OVA coated
Plate
Antigen-Delivery to Dendritic Cells: (Subcutaneous Route)
Targeting Toll Like Receptor (TL4)
Polysaccharide Backbone
TLR4 Ligand
Antigen-loaded
Biodegradable Nanoparticle
+
Proliferation Index (Post 3 Days)
Lipid A Anchor
0.5
Stimulation of Splenocytes from vaccinated
mice with OVA antigen
LPS Particles/OVA
0.45
0.4
0.35
Unmodified Particles/OVA
0.3
Blank Particles
0.25
0.2
0
50OVA (ug/ml)100
150
100-500 nm
Antigen-Delivery to Dendritic Cells: (Oral Route)
Targeting Toll Like Receptor (TL4)
Polysaccharide Backbone
TLR4 Ligand
100-500 nm
Antigen-loaded
Biodegradable Nanoparticle
+
Proliferation Index (Post 3 Days)
Lipid A Anchor
0.9
Oral Vaccination followed by OVA antigen
Stimulation of Splenocytes
0.8
0.7
0.6
LPS Particles/OVA
0.5
Unmodified Particles/OVA
0.4
0.3
0
Blank Particles
30
60
90
OVA (ug/ml)
120
150
Protection during Transport:
Surface modification with pH responsive polypeptides:
200-500 nm
pH < 5
Surface
modification
37 C
pH > 5
Elastin
37 C
(Expanded
State)
pH = 7
Elastin-Coated
nanoparticle
pH = 2
Drug released (mg)
0.02
No Elastin (pH= 2)
0.015
0.01
Elastin (pH=2)
0.005
0
0
20
40
60
Time (hrs)
80
100
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
D Mediating transport and recognition
100-400 nm
Encapsulated
antigen
subunit
Transepithelial
cell transport
Dendritic Cell
recognition
Encapsulated
Endosomal
disruptor
Recognition
elements
Adaptor
Endosomal Disruption
element
Biodegradable polymer
Antigen