The goal of this research is develop therapeutic products for Cryptosporidium parvum which can be made at a scale and cost which are feasible for delivery to large populations of patients or individuals at risk, as may be necessary in countering bioterrorism, or in protecting field-deployed armed forces. Our approach is to develop recombinant neutralizing monoclonal antibodies, and fusion proteins that genetically link monoclonal antibodies to parasiticidal proteins (biocides) which neutralize C. parvum sporozoites and merozoites. We will use a proprietary retrovector gene transfer technology to insert multicistronic gene constructs for the monoclonal fusion product candidates into cell culture. Following identification of products effective in vitro and in mouse models, we will scale up production in cell culture and by creation of transgenic cattle that express the monoclonal antibodies and fusion proteins in their milk and test anti-cryptosporidial efficacy in neonatal mice and pig models. Transgenic expression will enable manufacture of anti-cryptosporidial therapeutics economically and on a large scale. In addition to biodefense applications, the technology developed will also have important dual-use application in treatment of opportunistic infections with C. parvum and traveler's diarrhea, and in veterinary use to reduce the environmental reservoir of infection.
| Imboden, Michael; Schaefer, Deborah A; Bremel, Robert D et al. (2012) Antibody fusions reduce onset of experimental Cryptosporidium parvum infection in calves. Vet Parasitol 188:41-7 |
| Carryn, Stephane; Schaefer, Deborah A; Imboden, Michael et al. (2012) Phospholipases and cationic peptides inhibit Cryptosporidium parvum sporozoite infectivity by parasiticidal and non-parasiticidal mechanisms. J Parasitol 98:199-204 |
| Imboden, Michael; Riggs, Michael W; Schaefer, Deborah A et al. (2010) Antibodies fused to innate immune molecules reduce initiation of Cryptosporidium parvum infection in mice. Antimicrob Agents Chemother 54:1385-92 |
| Sturbaum, Gregory D; Schaefer, Deborah A; Jost, B Helen et al. (2008) Antigenic differences within the Cryptosporidium hominis and Cryptosporidium parvum surface proteins P23 and GP900 defined by monoclonal antibody reactivity. Mol Biochem Parasitol 159:138-41 |
