With the current emphasis on defined vaccines composed of protein subunits, there is a persistent need to improve the stability and performance of vaccines. Most vaccines are formulated in aqueous buffers and suspensions with aluminum salts adjuvants, vaccine immunogens degrade and lose potency (and efficacy). Elevated temperature increases the rate of protein degradation. As a result, liquid vaccines must be stored under refrigerated or frozen conditions. A well-controlled environmental cold chain must be maintained from the point of manufacture to the ultimate vaccinee. Temperature control will ultimately not be satisfactory in situations where vaccines are rarely used or not widely distributed especially where the vaccines are to be stockpiled for use for biodefense. The goal of this proposal is to develop processes and specific thermally stable formulations for two biodefense subunit vaccines adsorbed to aluminum adjuvants. This will be accomplished by using a drying technology and excipients that prevent the aggregation of aluminum adjuvant particles during freeze-drying and subsequent storage, while also preserving the structural and chemical integrity of the antigen. The vaccine subunits for study and development, a Ricin A chain vaccine (RTA V76M/Y80A, RiVax(tm)) and a hyperimmunogenic mutant (DNI, dominant negative inhibitor) of B. anthracis protective antigen (PA), are overall well characterized in physical and immunological properties. The first goal of this proposal is to develop and characterize the terminal step in manufacture of the vaccines, which would comprise lyophilization aluminum hydroxide-adsorbed subunit vaccines in the presence of stabilizing excipients, permitting retention of structure of the immunogens and functionality of the adjuvant. The second goal of this proposal is to develop vaccines that are more effective by employing well-characterized co-adjuvants that can be added to aluminum adjuvants subunits. This is expected to result in dried thermostable subunit vaccines that can be given in an accelerated regimen (fewer numbers of doses) and which result in more rapid onset of protective immunity.
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