Patrick Wilson, Ph.D.
Early Plasma Cells as a Source of Anthrax-Neutralizing Antibodies
We have developed a novel strategy to rapidly produce fully human monoclonal antibodies after immunization. These antibodies are derived recombinantly from expression of the immunoglobulin variable region genes of early antibody-secreting cells (ASCs) that arise in a massive but transient burst 7 days after immunization. This technology represents a substantial advance in monoclonal antibody production from humans. We have now used this strategy to produce a limited number of antibodies from recipients of the anthrax vaccine. We have subsequently used serological tools to identify several key peptide epitopes that effectively neutralize anthrax toxin activity (largely in collaboration with our colleague on this U19, Dr. Judith James). One central goal of this Technological Component is to isolate the monoclonal antibodies that target these epitopes. These antibodies could be developed for safe passive immunization to treat victims of anthrax infection. In addition, analyses of monoclonal antibody reactivity may identify protective antibody specificities that are not dominant in the polyclonal response, or that only arise against non-peptide, structural epitopes. Although a vaccine against anthrax is in limited use (to vaccinate military personnel, for example), its effectiveness has not been fully tested and it requires multiple and continued boosts to provide protection. Furthermore, our colleagues in this U19 have found that serum from only half of immunized soldiers can neutralize anthrax toxin. Thus a second goal of this project is to characterize the induction of long-term B cell immunity (memory) to gain insight into why the vaccine efficacy is variable.