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Vaccines are without doubt the most powerful approach currently available for the prevention of the deleterious effects of toxins and infectious agents that might be used in a bioterrorism against civilians or military personnel. Recent disclosures have indicated that numerous countries/or terrorists organizations may possess biological weapons that could indeed be used for this purpose. Likely, agents include anthrax, botulinum toxin, smallpox, tularemia, plague, and Venezuelan equine encephalitis. With the exception of plague, vaccines exist for all these agents. Unfortunately, at least in the case of anthrax, the vaccine is very unstable and is inactivated at 37C, limiting the ability to deliver the vaccine under battlefield conditions. It is probable the other vaccines will display similar instability. It is believed that this stability issue needs to be addressed by a systematic, molecular approach. The work in this grant investigated a systematic approach to the stabilization of vaccines utilized for the protection of civilians and military personnel against potential bioterrorism agents. Adenovirus was used as a model organism to study degradative pathways in viruses that could be responsible for thermal instability. Recombinant protein vaccine candidates against anthrax and valley fever were studied as the initial candidates for stabilization. This approach utilized a variety of physical methods (2nd derivative UV absorption spectroscopy, intrinsic and extrinsic fluorescence, circular dichroism, dynamic light scattering, differential scanning calorimetry etc.) to identify the molecular event(s) responsible for degradation of the vaccine components. This information was used to generate empirical phase diagrams that define different stability states for each vaccine. Once regions of stability were identified, high-throughput screening assays were developed based on phase boundaries and used to screen libraries of excipients to identify potential stabilizers.