Identification of Potential Vaccine and Drug Target Candidates by Expressed Sequence Tag Analysis and Immunoscreening ofOnchocerca volvulusLarval cDNA Libraries

• DOI: 10.1128/iai.68.6.3491-3501.2000
• Publication Date: 2002-07-27T09:58:18Z
• Authors: Michelle Lizotte-...; Wilson Tawe; David B. Guiliano; Wenhong Lu; Jing Liu; Steven A. Williams; Sara Lustigman
• Keywords: Immunoscreening

ABSTRACT The search for appropriate vaccine candidates and drug targets against onchocerciasis has so far been confronted with several limitations due to the unavailability of biological material, molecular resources, knowledge parasite biology. To identify or chemotherapy development we have undertaken two approaches. First, cDNA expression libraries were constructed from life cycle stages that are critical establishment Onchocerca volvulus infection, third-stage larvae (L3) molting L3. A gene discovery effort was then initiated by random expressed sequence tag analysis 5,506 clones. Cluster analyses showed many transcripts up-regulated and/or stage specific in either one both when compared microfilariae, L2, adult parasite. Homology searches GenBank database facilitated identification genes interest, such as proteinases, proteinase inhibitors, antioxidant detoxification enzymes, neurotransmitter receptors, well structural housekeeping genes. Other O. homology only predicted free-living nematode Caenorhabditis elegans entirely novel. Some novel proteins contain potential secretory leaders. Secondly, immunoscreening L3 library a pool human sera putatively immune individuals, identified six immunogenic otherwise would not vaccinogens using effort. This study lays solid foundation better understanding biology filaricidal agents vaccines based on immunological rational hypothesis-driven research.