Antibody-Biocide Fusions to Control Cryptosporidium

DESCRIPTION (provided by applicant): Cryptosporidiosis is a leading cause of diarrheal disease worldwide and is a category B biothreat agent. Two major species, Cryptosporidium hominis and Cryptosporidium parvum are responsible for over ninety percent of cases in man. C. parvum is zoonotic, with a reservoir in cattle, where it is an economically important cause of disease. There is currently no specific drug for cryptosporidiosis. The goal of this project is to bring to the point of readiness for out-licensing Directed BiocideTM therapeutics which target Cryptosporidium species affecting man and livestock and which are effective in oral treatment of cryptosporidiosis. The Directed BiocideTM approach creates a recombinant fusion protein in which an antibody targeting a surface epitope on Cryptosporidium sporozoites delivers an anticryptosporidial biocide comprising a natural antimicrobial peptide or enzyme to the surface of the sporozoite. With this approach Directed BiocideTM products are effective at far lower concentrations than a sporozoite-neutralizing antibody acting alone. Additional Directed BiocidesTM will be developed to target all causal species of human cryptosporidiosis, including C. hominis, and will be tested in vitro and in multiple animal models. Purification strategies will be established for these novel fusion protein products which will be suitable for human use products. The project also continues research to produce anticryptosporidial Directed BiocidesTM in milk of transgenic cattle for oral treatment of livestock or large populations. PUBLIC HEALTH RELEVANCE: Cryptosporidiosis is one of the most important causes of diarrheal disease worldwide, affecting both immunocompromised and immunocompetent individuals and sometimes causing mass outbreaks. Cryptosporidium is a Category B biothreat agent. Currently there is no effective drug available for cryptosporidiosis. This project develops a novel recombinant protein drug to neutralize the two species of Cryptosporidium that are responsible for over 90% of cases affecting humans.