(6ad) Mucosal Vaccine Delivery and Adjuvant Systems

Mucosal surfaces, i.e., surfaces that line the lumen and cavities of the human body such as the stomach, lungs and the mouth, form a portal of entry for majority of the pathogens including HIV and influenza virus. Very few pathogens such as the malarial parasite, which is injected by a mosquito, directly enter the human body. Defense from current intramuscular (IM) vaccines protects against pathogens only once they have entered the human body and does not protect against entry of pathogens from mucosal surfaces. However, mucosal vaccination (i.e., delivery of vaccines to mucosal surfaces) has the dual ability to protect against pathogen entry at mucosal surfaces and to defend against pathogens if they escape the mucosal immunity and enter the human body. Despite the potential of mucosal vaccination to induce a more robust immune response, difficulty in delivering vaccines across the tough mucosal barriers and lack of safe adjuvants (i.e., immune enhancing agents) has limited research and applications in the field of mucosal vaccines. But for these difficulties, many more mucosal vaccines could be commercialized and used. To facilitate mucosal vaccine delivery, the overarching goal of my proposed research is to enable targeted mucosal vaccine delivery across the mucosal barrier with the capability of modulating the resulting immune responses for diverse applications such as immunization against pathogens, allergy treatment, cancer treatment and the treatment of autoimmune diseases.

To achieve the overall goal, I will utilize fundamentals of science, engineering and immunology to develop medical applications in vaccine delivery and adjuvants. The research projects have been developed such that these fundamentals are applied in novel ways to solve medical problems while simultaneously developing upon these concepts. Initially I will focus on the oral mucosa (mucosa of the mouth) because it is easily accessible, and it can be conveniently targeted for permeability modulation and targeted vaccine delivery. Later, other mucosal surfaces such as the nose and the vagina will also be studied.

I initially propose to (i) develop a novel method to permeabilize the oral mucosa and optimize the process using principles of fluid dynamics, (ii) investigate physcial adjuvants for their effect on the oral mucosal vaccination, and (iii) conduct fundamental research to characterize and quantify the response of oral mucosal immune cells to different stimuli. Because I am proposing a novel method to permeabilize the oral mucosa, I have generated preliminary data to demonstrate the feasibility of this novel approach. In my poster presentation I will discuss these research projects in greater depth.