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Identification of potential vaccine and drug target candidates by expressed sequence tag analysis and immunoscreening of Onchocerca volvulus larval cDNA libraries.

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, 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.
AuthorsM Lizotte-Waniewski, W Tawe, D B Guiliano, W Lu, J Liu, S A Williams, S Lustigman
JournalInfection and immunity (Infect Immun) Vol. 68 Issue 6 Pg. 3491-501 (Jun 2000) ISSN: 0019-9567 [Print] United States
PMID10816503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibodies, Helminth
  • Antigens, Helminth
  • Filaricides
  • Receptors, Cell Surface
  • Receptors, Neurotransmitter
  • Vaccines
  • Endopeptidases
  • Peptidylprolyl Isomerase
Topics
  • Animals
  • Antibodies, Helminth (blood)
  • Antigens, Helminth (genetics, isolation & purification)
  • Endopeptidases
  • Expressed Sequence Tags
  • Filaricides (metabolism)
  • Gene Expression Profiling
  • Gene Library
  • Genes, Helminth
  • Humans
  • Larva (enzymology, genetics, immunology)
  • Molecular Sequence Data
  • Onchocerca volvulus (enzymology, genetics, immunology)
  • Onchocerciasis (immunology)
  • Peptidylprolyl Isomerase (genetics)
  • Receptors, Cell Surface (genetics)
  • Receptors, Neurotransmitter (genetics)
  • Sequence Homology, Amino Acid
  • Technology, Pharmaceutical
  • Up-Regulation
  • Vaccines

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