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Infection and Immunity, June 2000, p. 3491-3501, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Identification of Potential Vaccine and Drug Target Candidates by Expressed Sequence Tag Analysis and Immunoscreening of Onchocerca volvulus Larval cDNA Libraries

Michelle Lizotte-Waniewski,1,2 Wilson Tawe,3 David B. Guiliano,4 Wenhong Lu,1,2 Jing Liu,3 Steven A. Williams,1,2 and Sara Lustigman3,*

Program in Molecular and Cellular Biology, University of Massachusetts, Amherst,1 and Department of Biological Sciences, Clark Science Center, Smith College, Northampton,2 Massachusetts; Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York3; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom4

Received 30 November 1999/Returned for modification 11 January 2000/Accepted 17 March 2000

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

* Corresponding author. Mailing address: Lindsley F. Kimball Research Institute, New York Blood Center, 310 E. 67th St., New York, NY 10021. Phone: (212) 570-3119. Fax: (212) 570-3121. E-mail: slustigm{at}nybc.org.

Infection and Immunity, June 2000, p. 3491-3501, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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