The long term goal of this proposal is to develop a novel targeted vaccine technology against emerging infectious diseases and pathogens associated with bioterrorism. Previous studies have documented the extremely rapid and potent immune responses elicited by vaccines that target antigens specifically to professional antigen presenting cells (APCs). In addition to induction of rapid and robust immune responses targeted vaccines have the potential to be safer, easily administered, and require very low doses for a more cost-effective product. We have developed a human monoclonal antibody (mAb) specific for mannose receptors (MRs) that are abundantly expressed on dendritic cells(DCs) and other APCs, as a delivery vehicle or antigen targeting. Antigens linked to this mAb are efficiently presented and induce potent antibody and cytotoxic T lymphocyte responses. In this application, we propose to develop and test a targeted vaccine for prevention and treatment of anthrax by attaching the anthrax protective antigen to our MR mAb. We hope to demonstrate induction of toxin neutralizing antibodies within days of immunization in rodents and primates, which will justify further development of the vaccine in spore challenge models. Vaccine efficacy will be assessed after intramuscular or nasal delivery using a well established toxin neutralization assay. Successful completion of the project would result in an easily administered, cost-effective vaccine that would be useful or the vaccination of individuals 1) suspected of exposure, 2) at high risk of near-term exposure, 3) and possibly after appearance of anthrax related symptoms. Such a vaccine could also greatly reduce the course of antibiotics that is currently given to potentially exposed individuals. Furthermore, in his vaccine would serve as a prototype for application of this technology to other important infectious disease pathogens where a fast acting vaccine is needed.
