The existing anthrax vaccine, AVA, causes serious side effects and requires multiple immunizations, precluding preventive vaccine prophylaxis when faced with an anthrax bioterrorist threat. Though recombinant anthrax protective antigen (PA) immunity may provide a substantial level of protection against infection, PA-based vaccine candidates utilize adjuvants not approved for human use. We propose to design and develop next generation recombinant anthrax vaccines with intrinsic adjuvant capabilities, based on multiple presentation of PA epitopes on the surface of self-assembling virus-like particles (VLP). A rational approach to designing PA-VLP chimeric vaccines is now possible due to the recently solved high-resolution structures of both PA protein and hepatitis B core (HBc) particle-the most prominent VLP carrier. There is also substantial progress in functional and immunogenic descriptions of the PA protein. We will combine this knowledge with advanced molecular modeling to ensure folding and assembly of functional VLP with optimal PA epitope display. This feasibility study is a platform work which will legitimize the approach while providing an effective vaccine. Nontoxic and non-infectious recombinant PA-HBc chimeric protein will be further developed as a vaccine. Successful PA-HBc design would provide a basis technology for inclusion of other components of anthrax virulence into the VLP vaccine formulation without compromising safety or production cost.
