Scientific Report 2007

Chemistry

Worm Institute for Research and Medicine

T.J. Dickerson, J. Denery, L. Eubanks, A. Hoyt, S. Mahajan, A. Moreno, J. Park, N. Salzameda, K.D. Janda

Although rare in the United States, in many other parts of the world, infections caused by filarial worms (nematodes) afflict hundreds of millions of people with painful, disfiguring, and debilitating diseases, including onchocerciasis, lymphatic filariasis, and dracunculiasis. Through the generous donation of John J. Moores, the Worm Institute for Research and Medicine was established to investigate the basic science needed for the development of diagnostic tools to efficiently detect the presence of parasitic worms in a person's body. These new diagnostic tests will be a powerful tool for public health practitioners and may ultimately lead to unique approaches for the treatment of filiarial infections throughout the world.

Onchocerciasis, or river blindness, is caused by the nematode Onchocerca volvulus (Fig. 1). In severe infections, the worms can cause lesions and massive inflammation in the eyes, ultimately leading to blindness. Onchocerciasis is a major problem in many African nations, where 99% of all cases occur. Although much effort has been devoted to regional programs to reduce the risk for this disease, significant obstacles, including improvement of current diagnostic methods, must be overcome before eradication is successful. Great strides in detection have been made by using various assays, including skin biopsies, detection of O volvulus DNA, and antibody-based strategies for detecting specific O volvulus proteins. However, none of the current methods can be used to detect sexually mature worms.

Fig. 1. A live female O volvulus worm extracted from a human nodule.

Major sperm protein (MSP) is the main component of nematode sperm and is critical for sperm motility. Because MSP is a unique feature of nematode reproduction, we propose that it is a potential target for diagnosis of nematode infections. In addition, antibody-mediated disruption of MSP polymerization may inhibit nematode reproduction. During the past year, we successfully cloned and expressed MSP from O volvulus and confirmed the dimeric character of the protein in solution. This recombinant MSP has been used both in screens of phage-displayed combinatorial antibody libraries and in traditional immunization procedures to isolate antibody reagents that can be used to detect MSP in the serum of patients with onchocerciasis.

Using serum samples collected from individuals of the Northwest Province of Cameroon, we determined that MSP is indeed released from the worm and that the protein is recognized by the immune system, resulting in significant antibody titers against MSP. We are optimizing the assay conditions to detect MSP directly by using our monoclonal antibodies.