Microspheres--Water-Soluble Polymers as Vaccine Vehicles

Modern molecular biology has provided us with a means of producing immunogens withunprecedented ease and precision, but these new methodologies generate purified immunogens that donot generally induce a strong immune response in the absence of an effective adjuvant. Thedevelopment of improved vaccine adjuvants for use in humans has therefore become a priority area ofresearch. Nevertheless, research on adjuvants has lagged seriously behind the work done onimmunogenes. For decades the only adjuvant widely used in humans has been alum. Saponin and itspurified component Quil A, Freund's complete adjuvant and other adjuvants sued in research andveterinary applications have toxicities which limit their potential use in human vaccines. New chemicallydefined preparations such as muramyl dipeptide and monophosphoryl lipid A are being studied. TheVirus Research Institute is interested in the development of vaccines to combat infectious disease. Amajor focus is the study of delivery systems and adjuvants that will induce a state of systemic immunity.Microencapsulation is the core technology in this endeavor. An area of adjuvant research that hasdeveloped over the last few years is the utilization of synthetic polymers such as polylactide-co-glycolide(PLGA) in the formulation of a vaccine to effect the controlled release of antigens. The cleardisadvantage of this polymer is the required use of organic solvents that are detrimental to labileantigens. The overall goal of the SBIR Phase I work is to develop a microsphere configured vaccinevehicle based on a water soluble polyphosphazene polymer. This goal will be accomplished byoptimizing both the generation of 1-10 micron diameter microspheres for each of five polyphosphazenepolymers and determining the dose and route to administration that maximize the rapidity, amplitude andduration of the antibody response to a single antigen dose. The distribution of the antibody responseover the IgG subclasses and the cellular immune response will be determined. Finally, the protectiveefficacy of the polyphosphazene microsphere immunization regimen in an animal model will be evaluated.