An improved targeted vaccine strategy against anthrax

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NERCE PROJECT 9: An improved targeted vaccine strategy against anthrax -Ronald K. Taylor, Ph.D. The goal of this proposal is to initiate the development of a novel, targeted vaccine technology against pathogens associated with bioterrorism and those that are responsible for emerging infectious diseases. Extremely rapid and potent immune responses are elicited by vaccines that target antigens specifically to professional antigen-presenting cells (APCs). In addition to inducing rapid and robust immune responses, targeted vaccines are potentially safer, easily administered, and require very low doses that leads to reduced cost. This project is based on a partnership between academic investigators and industry. Antigens will be targeted to dendritic cells (DCs) and other APCs using a monoclonal antibody (mAb) specific to the endocytic receptors, DEC-205 and mannose receptor (MR). These antibodies are rapidly internalized and gain access to the antigen presenting pathways. Antigens delivered in this way elicit potent antibody and cytotoxic T lymphocyte responses. Recombinant antigens will be chemically crosslinked and/or genetically fused to the mAbs using available human anti-DEC-205 and anti-MR gene fusion vectors. In the past year, we have fused recombinant protective antigen (rPA) of anthrax to anti-DEC-205 and tested the ability of the fusion to elicit humoral immune responses in mice. We are proceeding to apply the same strategy using anti-MR to develop a targeted vaccine for cholera, using recombinant TcpA from Vibrio cholerae.