Projects

Development of Ovalbumin Nanoparticles in Squalane Oil Multiple Emulsion Oral/Intranasal Delivery System for DNA Tuberculosis Vaccine Delivery

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Abstract

The purpose of my research is to develop a non-invasive delivery system for the administration of a DNA vaccine for protection against Mycobacterium tuberculosis (TB) infection. TB is a pulmonary infection that is the direct cause of death for two million people each year, and a total of three million people when HIV+ individuals who die with active TB are included. The only vaccine currently available for Tuberculosis is the bacillus Calmette-Guerin (BCG) vaccine, which is unable to protect adults and immunodeficient individuals from infection, severely minimizing its effectively. The worldwide severity of this disease demonstrates the need for a potent and effective vaccination.

The following research project proposes to use a plasmid DNA vaccine to induce a protective immune response against TB. However, without a protective and targeted delivery system, plasmid DNA vaccines have a low degree of cellular uptake and tranfection, and will likely be degraded and eliminated before reaching target tissue. The use of particle-mediated DNA vaccine delivery increases stability of DNA, cellular uptake, and can allow targeting to specific cells. In addition, the proposed delivery system will allow oral or intranasal administration of the vaccine. This can result in greater availability and use, especially in areas where administration by injection can be hazardous due to the high prevalence of HIV and communicable diseases. This project will evaluate the potential of ovalbumin nanoparticles in a squalene oil multiple emulsion system for the targeted delivery of Ag85 and PStS3 encoding plasmid DNA vaccines.

The preliminary studies of this research project will include the formulation and characterization of the nanoparticle-containing multiple emulsion delivery system, followed by in vivo studies using C57 mice. The second major step in this research project will be to conduct in vivo studies of the gastrointestinal distribution and Peyer’s patch accumulation. Once the preliminary studies have been completed, the experimental design and methods portion of this research project will evaluate the mucosal and systemic immune response to oral and intranasal vaccination, and final vaccine efficacy studies will be conducted in a TB challenge model.