Nanoparticle Technology for Minimally-invasive Delivery of DNA Vaccines

Venezuelan equine encephalitis virus causes an acute debilitating disease in humans characterized by fever, mylagia, headache, lymphopenia and malaise and can also lead to neurological symptoms and encephalitis. The highly pathogenic strains are frequently associated with epidemics in North Central and South America and VEEV is classified as a category B select agent. Vaccines against VEEV have been elusive in that live attenuated vaccines produce life long immunity in some and no detectable immune response or adverse effects in others. Inactivated virus fails to protect against aerosol challenge. A DNA vaccine under intensive testing in different formulations and routes of delivery has had promising but incomplete success. Particle mediated epidermal delivery (PMED) of the vaccine is the most promising yet but has not protected all subjects. We propose a method for delivery of the existing DNA vaccine using a controlled release nanoparticle that provides a continual boosting effect through increased levels of antigen uptake and presentation. Controlled release particles developed in our labs have dramatically enhanced efficacy of safe but poorly performing vaccines. We propose a nanoparticle delivery platform to improve efficacy of the VEEV DNA vaccine and permit ease of delivery through PMED or intranasal administration.