1 STRUCTURAL CHARACTERIZATIONS OF PROTEIN ANTIGENS FOR THE NEXT- GENERATION VACCINES AGAINST ANTHRAX AND PLAGUE

Two recombinant protein antigens called rPA and F1-V are recommended by the U. S. Army as active pharmaceutical ingredients (API) for the next-generation vaccines to protect the warfighter against aerosolized anthrax and plague. Separate candidate vaccines containing purified antigen bound to aluminum hydroxide adjuvant in phosphate-buffered saline (PBS) have been tested at the research level, and each has satisfied requirements for advancement to product development. These criteria included: demonstrations of direct and surrogate efficacy in respective animal disease models; preliminary assessment of product safety by testing acute toxicity and API stability; demonstration of an in vitro correlate of protection for development as a potency test; and proposed baseline methods from which to develop a robust manufacturing process and assays for testing product purity, quality, strength, and stability. USAMRIID scientists provided the discovery and concept research in this regard for both candidate vaccines and have been performing ongoing supportive basic research to further the eventual translation of each into a viable product. In looking forward, one of many U. S. Food and Drug Administration (FDA) requirements for eventual human use of these vaccines is documentation of progressive studies that increase understanding of the chemical and biophysical properties of the API. Each of these two protein antigens exhibited unexpected physical features early in research that required further definition. This paper summarizes our characterizations of observed heterogeneity within these pure vaccine proteins: in primary structure for the rPA antigen; and in quaternary structure for the F1-V antigen. This work also illustrates the value of extending technology base research beyond the stages of discovery and proof of concept so as to better support the creation of medical biological products that will protect the warfighter against biological threats