A great deal of effort has been directed towards developing nonparenteral (needle-free) alternatives to traditional vaccine delivery. Nonparenteral vaccines offer a number of potential advantages over traditional vaccines including 1) the potential to confer mucosal as well as systemic immunity, 2) increased stability, 3) increased shelf-life, 4) elimination of needles and the need for specially trained healthcare specialists to administer vaccines, and 5) potentially lower costs. One such approach, transcutaneous immunization (TCI), is a non-invasive, safe method of delivering antigens directly onto bare skin. Immunization is achieved by direct topical application of a vaccine antigen. Despite the attractiveness of TCI, the technology is limited by the relative inefficiency of transport of large molecular weight vaccine antigens across intact skin. Recent innovations in transdermal delivery of drugs, including chemical enhancers, electricity, ultrasound, and microneedles, demonstrate the feasibility of large-molecule transport through the skin's permeation barrier, specifically the stratum corneum. This outer layer of the skin is composed of tightly packed lipid molecules and the dense, crystalline arrangement of these lipids creates the essential barrier to prevent water loss and pathogen entry. Recent evidence has shown that this barrier can be overcome by properly structured nano-sized particles (nanocarriers). This proposal will compare three different nanocarriers (temperature-responsive hollow nanospheres, nanohydrogels, and star copolymers) for the ability to incorporate a model vaccine antigen and deliver that antigen through the stratum corneum to immunoresponsive cells in the epidermis. The specialized assembly of each type of nanocarrier gives each unique properties and different interactions within the lipid channels of the stratum corneum. The use of nanocarriers for vaccine delivery is a platform technology, applicable to delivery of a variety of existing and potential vaccines. For the purposes of this proposal, we will utilize two different proteins: 1) Bovine Serum Albumin that has been fluorescently labeled to monitor incorporation and permeation of a macromolecular antigen, and 2) F1-V, a vaccine antigen from Yersinia pestis, the causative agent of plague, which we and others have shown to protect against aerosol challenge with virulent Y. pestis. The proposed studies will address important questions in vaccine delivery by application of nanotechnology through the exploitation of the novel properties of nanocarriers. The findings of these studies will be broadly applicable to a variety of vaccines and therapeutics and will further highlight the important role of nanotechnology in science and medicine. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB006493-02
Application #
7208002
Study Section
Special Emphasis Panel (ZRG1-BCMB-R (50))
Program Officer
Henderson, Lori
Project Start
2006-04-01
Project End
2010-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
2
Fiscal Year
2007
Total Cost
$492,665
Indirect Cost
Name
Tulane University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Norton, Elizabeth B; Lawson, Louise B; Mahdi, Zaid et al. (2012) The A subunit of Escherichia coli heat-labile enterotoxin functions as a mucosal adjuvant and promotes IgG2a, IgA, and Th17 responses to vaccine antigens. Infect Immun 80:2426-35
Dhule, Santosh S; Penfornis, Patrice; Frazier, Trivia et al. (2012) Curcumin-loaded ?-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma. Nanomedicine 8:440-51
Wang, Qing; Jaimes-Lizcano, Yuly A; Lawson, Louise B et al. (2011) Improved dermal delivery of FITC-BSA using a combination of passive and active methods. J Pharm Sci 100:4804-14
Poree, Dawanne E; Giles, Marco D; Lawson, Louise B et al. (2011) Synthesis of amphiphilic star block copolymers and their evaluation as transdermal carriers. Biomacromolecules 12:898-906
Jaimes-Lizcano, Yuly A; Lawson, Louise B; Papadopoulos, Kyriakos D (2011) Oil-frozen W?/O/W? double emulsions for dermal biomacromolecular delivery containing ethanol as chemical penetration enhancer. J Pharm Sci 100:1398-406
Li, Yejia; Giles, Marco D; Liu, Simin et al. (2011) A versatile and modular approach to functionalisation of deep-cavity cavitands via""click"" chemistry. Chem Commun (Camb) 47:9036-8
Norton, Elizabeth B; Lawson, Louise B; Freytag, Lucy C et al. (2011) Characterization of a mutant Escherichia coli heat-labile toxin, LT(R192G/L211A), as a safe and effective oral adjuvant. Clin Vaccine Immunol 18:546-51
Li, Yejia; Hoskins, Jessica N; Sreerama, Subramanya G et al. (2010) The identification of synthetic homopolymer end groups and verification of their transformations using MALDI-TOF mass spectrometry. J Mass Spectrom 45:587-611
Wang, Qing; Tan, Grace; Lawson, Louise B et al. (2010) Liposomes in double-emulsion globules. Langmuir 26:3225-31
Tan, Grace; Xu, Peng; Lawson, Louise B et al. (2010) Hydration effects on skin microstructure as probed by high-resolution cryo-scanning electron microscopy and mechanistic implications to enhanced transcutaneous delivery of biomacromolecules. J Pharm Sci 99:730-40

Showing the most recent 10 out of 19 publications