Stabilization of Influenza Vaccine by Silica-Coating

The goal of this Phase I STTR grant proposal is to stabilize live attenuated influenza vaccine LAIV using a temporary silica coating that is removed in vivo In so doing we will establish a broader technology to eliminate the cold chain required for transport of heat and cold labile vaccines Many vaccines are unstable under ambient environmental conditions Currently vaccines are either stabilized in liquid formulations and must be kept between C or are lyophilized stored frozen and then reconstituted just before use Maintaining the cold chain demands great expense and logistic issues for distribution with the result that an estimated million children die each year worldwide from vaccine preventable diseases We have developed a proprietary technology to reversibly inactivate a wide variety of viruses by coating them with silica The coating confers the viruses with extraordinary tolerance to dessication This coating is completely reversible and dissolves in vivo rendering the viruses once again effective as vaccines in a preliminary test both silica coated and uncoated vaccinia virus induced similar T cell mediated immune responses in vivo in a murine model We hypothesize that we can silica coat live attenuated influenza vaccine and that this coating will stabilize the vaccine suspension at ambient temperatures eliminating the need for refrigeration or freezing To establish proof of concept we propose three aims in Phase I Aim Coat and uncoat LAIV with silica Aim Show that coated LAIV is stabilized in vitro Aim Show that coated LAIV replicates and generates an immune response in vivo At the conclusion of this Phase I STTR project we will have reached our Milestones showing that we can coat LAIV and the coating protects the vaccine from inactivation yet still causes an immune response Thereby we will have established proof of concept for silica coating of vaccines without loss of immunogenicity and will be poised to launch Phase II in which we will work directly with vaccine manufacturers and developers to stabilize their vaccines and vaccine candidates develop industrial scale coating processes show that coated vaccines confer protective immunity and perform toxicity testing to support regulatory filing Many vaccines are unstable unless they are kept cold but maintaining the cold chain during shipping and storage is expensive and is subject to failures that render the vaccine ineffective or unusable We propose here to employ a novel technique to stabilize Live Attenuated Influenza Vaccine with a reversible silica coating If successful this technique could be employed more widely on other vaccines to save money and lives by allowing more facile distribution and less wastage