Modular Nanodevices for Creation of Smart Adaptable Vaccine Delivery Vehicles

1
Modular Nanodevices for Creation of Smart
Adaptable Vaccine Delivery Vehicles Tarek M.
Fahmy Dept. of Biomedical Engineering, Yale
University
SUMMARY We describe a generalizable smart
nanoparticle vaccine delivery system using a
simple, modular approach that can be easily
adapted to the requirements of a particular
vaccine. Our approach tethers individual DC
recognition, Transepithelial and protective
elements into the surface of the nanodevice
constructed from biocompatible polyester poly
(lactic-co-glycolic acid) (PLGA). The core of the
device is loaded with antigen or elements
facilitating targeted release of antigen into the
correct intracellular compartments. In this work
the use of biodegradable polymer nanoparticles as
a platform for designing vaccines is being
systematically and quantitatively explored.
In Vivo Vaccination Enhanced Antigen-Specific
Cellular Proliferation with DC targeted
nanoparticle vaccines
SUBCUTANEOUS VACCINATION
Particle size was analyzed using SEM images and
were found to be an average of 100-200 nm.
Ovalbumin (OVA) was encapsulated as the model
antigen and a release profile (insert) was
deduced using a protein assay.
Targeting Dendritic Cells
ORAL VACCINATION
Blank Particles
LPS/Particles
Several key variables are needed in the design
of effective vaccines (Figure 1). The first
variable is the form of the antigen itself. A
second necessary component of a vaccine involves
potentiating or stimulating the innate and
adaptive arms of the immune system to the antigen
subunit. Finally, to affect optimal stimulation
to a given antigen a formulation is needed that
delivers the correct amount of antigen in a
repetitive or sustained fashion, to the
appropriate immune cells and to the appropriate
compartments within those cells.
Lipopolysaccharide modified nanoarpticles
encapsulating a dye are preferentially
internalized by dendritic cells
Proliferation of spleen cells from mice
subcutaneously or orally vaccinated with
ovalbumin-encapsulating nanospheres.. Isolated
spleen cells were challenged with different doses
of ovalbumin antigen in a plate. Nanospheres
modified with LPS encapsulating OVA , nanospheres
encapsulating OVA with no external modification
(Untargeted ), blank particles with no OVA and no
surface modification (No OVA). Mice (N3)
In Vitro Vaccination Effective Antigen-Specific T
cell Proliferation in vitro with DC targeted
nanoparticles
LPS-OVA
Vaccination against the West Nile Virus E-Protein
P lt 0.0035
Untargeted
Soluble OVASoluble LPS
No OVA
OBJECTIVES 1) Engineering individual
nanoparticulate recognition units that
effectively target DCs. 2) Examination of the
uptake of the nanodevice by cultured dendritic
cells and determining the efficacy of antigen
presentation. 3) Engineering nanoparticulates to
transit through epithelial cell layers. 4)
Engineeringsmart protective coatings
facilitating transport through low pH and
corrosive environments.
Dendritic cells were isolated and primed with
blank nanospheres (No OVA ), unmodified OVA
particles (Untargeted), LPS-modified OVA
nanospheres (LPS-OVA), blank nanospheres with
soluble OVA (Soluble OVA), or blank nanospheres
with soluble OVA and soluble LPS (Soluble OVA
Soluble LPS) and co-cultured with splenocytes
from an OT-1 transgenic mouse. IL-2 release was
measured by ELISA.
Work supported by NSF-NIRT Award 0609326