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Toward ideal vaccines for emerging and biothreat agents
Institution: Arizona State University (ASU), Tempe, AZ
Principal Investigator: Kathryn Sykes, PhD
Co-Investigator: Alexandre Borovkov, PhD – ASU, Tempe, AZ
Expected Product:New technologies for vaccine discovery, production, and administration.
Description: Emergence of challenging new infectious agents and concern for biothreat deployment has highlighted needs for new technologies in vaccine discovery, production, and administration. The advantages of gene vaccines make it the likely basis for many of these new developments. However, the major drawback has been their generally low immunogenicity. In some cases one or more of a variety of adjuvants have been able to enhance response levels; however, each antigen and adjuvant combination must be empirically identified. We propose to develop a single-platform approach to delivering any gene vaccine that will improve delivery efficiency, raise immune potency, and broaden mucosal responsiveness, without adjuvant. This approach is based on the high immunogenicity of viral particles, and the flexibility of a genetic modality. We will test a genetic approach to simply build and flexibly deliver highly immunogenic antigens presented on the surface of viral-like particles (VLPs). These will be designed to target specific classes of antigen presenting cells (APCs) and be effectively delivered via either systemic or mucosal routes. The anthrax PA, influenza HA, and vaccinia B5R antigens will be used as models. The genetically delivered VLP formats will be benchmarked to gene and classical protein subunit vaccines. Once immune stimulation profiles have been determined, the utility of the VLPs as vaccines will be evaluated in animal models of disease. If successful, this project will provide the lynchpin toward the goal of rapidly designing, producing, and administering safe and broadly efficacious vaccines to both emerging and biothreat diseases. |
