Coupling a broadly applicable antibody discovery technology with a rapid, scalable manufacturing platform, human monoclonal antibody (Mab) immunoprotectants against two Category B Select Agents, Clostridium perfringens (CP) epsilon toxin (ETX) and staphylococcal enterotoxin B (SEB) will be developed. The synergistic effect of pursuing products against both toxins on a common discovery and manufacturing platform will manifest as savings in costs and time. This project will serve as a proof-of-concept for these platforms which should be generalizable for the development of human Mab immunoprotectants against other bio-warfare agents, as well as newly emerging and re-emerging infectious diseases. In Specific Aim 1, we will evaluate a panel of human anti-ETX and anti-SEB Mabs in vitro. The best neutralizers will be evaluated in Specific Aim 2 in mouse models of ETX and SEB intoxication. The three best Mabs against each toxin will be produced in a Nicotiana benthamiana manufacturing system in Specific Aim 3, and the lead Mab for ETX and SEB will be selected based on in vivo activity, expression, and stability data. In Specific Aim 4, all IND-enabling activities will be completed with a final goal of submitting INDs for each product candidate. The long-term objective of this effort is the commercialization of anti-ETX and anti-SEB Mabs. The envisioned immunoprotectants will be injectable, for prophylaxis and/or therapy in humans. The final commercialized product will be a lyophilized formulation (to be reconstituted immediately prior to injection) to maximize stability across a wide range of environmental conditions.