We have developed techniques for the production of monoclonal secretory IgA's using a plant-based expression system. The inherent stability of these antibodies coupled with the potential for large scale agricultural production offers an entirely new approach to the treatment of enteric diseases. The overall goal of this project is to express therapeutic secretory antibodies for enteric pathogens in edible plants. In phase I, the heavy and light chain genes from a cross-neutralizing murine monoclonal antibody to rotavirus were cloned and sequenced. This antibody administered by mouth previously was shown to block diarrhea in mice infected with human rotavirus. In phase II the V-regions will be transferred to our plant vector. Transgenic alfalfa will be generated using these clones as well as clones for J chain and secretory component. The assembled secretory antibody will be evaluated as both a crude plant extract as well as in purified form in a murine model of rotavirus infection. Successful production of therapeutic antibodies in plants offers many attractive advantages over fermentation, among them cost, ease of administration, safety and efficacy. This approach will provide a novel and inexpensive means to make and deliver antibodies to prevent or treat a number of important human or animal gastroenteric pathogens.
Neutralizing anti-rotavirus plantibodies will have prophylactic or therapeutic value for rotavirus diarrhea disease. This general method to generate therapeutic plantibodies will be applicable to many human or animal gastroenteric pathogens that cause viral and bacterial diarrheas, hepatitis and gastritis.
