Modular Nanodevices for Creation of Smart Adaptable Vaccine

Modular Nanodevices for Creation of Smart Adaptable Vaccine

Modular Nanodevices for Creation of Smart Adaptable Vaccine
Delivery Vehicles
Tarek M. Fahmy
Dept. of Biomedical Engineering, Yale University

In Vivo Vaccination

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.

Enhanced Antigen-Specific Cellular Proliferation with
DC targeted nanoparticle vaccines

OVA Release

% Total OVA Released














Proliferation x105

Time, hr

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


Blank Particles


Proliferation x105





Effective Antigen-Specific T cell Proliferation in
vitro with DC targeted nanoparticles







Vaccination against the West Nile Virus E-Protein

P < 0.0035 200 SubQ 150 100 50 Soluble OVA+Soluble LPS No OVA 0 -50 0 0.01 0.02 0.03 0.04 0.05 0.06 OVA Concentration (mg/ml) Dendritic cells were isolated and primed with blank nanospheres (No OVA ), unmodified OVA particles (Untargeted), LPS-modified OVA nanospheres (LPSOVA), 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. % Surviving Animals IL-2 Release (pg/ml) LPS-OVA 300 0 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 (N=3) In Vitro Vaccination 350 No OVA OVA (ug/ml) Lipopolysaccharide modified nanoarpticles encapsulating a dye are preferentially internalized by dendritic cells 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. 100 ORAL VACCINATION 0.9 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. OBJECTIVES 50 100 90 Oral 80 70 60 No Vaccine 50 40 N=10 per group Animals injected with live virulent virus on day 0. 30 20 10 Days Post Challenge 0 0 5 10 15 20 Work supported by NSF-NIRT Award: 0609326

Recently Viewed Presentations

  • Deadlocks System Model  There are non-shared computer resources

    Deadlocks System Model There are non-shared computer resources

    Deadlocks System Model There are non-shared computer resources Maybe more than one instance Printers, Semaphores, Tape drives, CPU Processes need access to these resources Acquire resource If resource is available, access is granted If not available, the process is blocked...
  • Jan 28, 2020 Design of Experiments Instructor: Ron

    Jan 28, 2020 Design of Experiments Instructor: Ron

    LIST POSSIBLE ANSWERS * FOR THE EXPERIMENT, EACH TEAM WILL NEED: Paper helicopter templates, scissors, paper clips Stopwatch Pen for writing on overhead cells Deck of 8 cards (1 - 8) for generating random numbers Calculators EXPLAIN: The design team's...
  • LegalShield Presentation

    LegalShield Presentation

    You signed up for $99 and now you own your own LegalShield independent business. You're going to start out as a LegalShield Associate. When you Market a $44.90 plan, and process that through, the company receives $44.90 it then turns...
  • NONFICTION: - Miss Lee&#x27;s Class Website

    NONFICTION: - Miss Lee's Class Website

    when an author gives personal opinions in a story or news report; often causing the reader to form a certain opinion Emotional Language/Semantic Slanting Emotional Language *loaded words that impact the reader's opinion/feelings Semantic Slanting *a technique that an author...
  • Energy Performance Contracts

    Energy Performance Contracts

    "Over 90% of the total energy for polystyrene foodservice products is from fossil fuels. This includes not only the use of fossil fuels for process and transportation energy, but also the energy content of the crude oil and natural gas...
  • Transgression, gift, sacrifice

    Transgression, gift, sacrifice

    The Piglet lived in a very grand house in the middle of a beech-tree, and the beech-tree was in the middle of the forest...Next to his house was a piece of broken board which had: "TRESPASSERS W" on it. When...
  • Making a Dichotomous Classification Key

    Making a Dichotomous Classification Key

    Arial Comic Sans MS Times New Roman Default Design MAKING A DICHOTOMOUS CLASSIFICATION KEY Slide 2 POSSIBLE "DERIVED CHARACTERS" Slide 4 Slide 5 Slide 6 Slide 7 Slide 8 Slide 9 WHAT'S IN A NAME? What's in a name? What's...
  • Nerve activates contraction

    Nerve activates contraction

    Chapter 3 continued … PART bV. The Plasma Membrane-- Transport. Terms To Fill Into PPT prior to Class. semipermeable, solvent, solute, Intercellular, extracellular, and interstitial fluids