HUMAN MONOCLONAL ANTIBODIES TO CATEGORY A PATHOGENS

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Historically it has been very difficult to generate IgG antibody secreting human immortalized B cells that produce significant amounts of antibody. This has been a major stumbling block to the study of human B cell immunology, and the understanding of human neutralizing antibodies. Additionally, neutralizing antibodies can be valuable therapeutic agents. It has recently been demonstrated that human hybridomas can be made that secrete substantial amounts of antibodies, using the human myeloma cell line Karpas 707H. Using this new technology, we propose to isolate anthrax antigen-specific B cells from inhalation anthrax infected human subjects (infected during the bioterrorism attacks of 2001), cutaneous anthrax cases, and AVA vaccinated human volunteers, and generate a panel of anti-anthrax antibody secreting B cell hybridomas from each of these groups. Monoclonal antibodies from these hybridomas will be studied for their anthrax protein specificity, binding characteristics, and neutralization properties. In addition, we propose to isolate and characterize smallpox-specific B cell hybridomas from smallpo vaccine (Dryvax) immunized individuals. Monoclonal antibodies (mAbs) obtained from these hybridomas should serve as invaluable reagents for understanding antibody-mediated protection against these two pathogens, which are both of major concern as bioterrorism agents. Additionally, human anti-anthrax neutralizing mAbs may serve as a source for producing large quantities of neutralizing antibodies for passive immunization of non-vaccinated subjects exposed to inhalation anthrax. Human smallpox neutralizing mAb producing hybridomas may serve as a source for producing large quantities of neutralizing smallpox antibodies for passive immunization of nonvaccinated subjects exposed to smallpox.