In the study of the human filariases, progress has been hampered by 1) the lack of defined parasite antigens; 2) the broad immunological cross- reactivity seen among the eight filarial species of humans; and 3) the dearth of abundant parasite material. The objectives of this project are to define and generate filarial proteins that are important in inducing parasite-specific immune responses in the human host and to understand, at a molecular level, the differences among related filarial species. cDNA and genomic libraries have been either constructed (Brugia malayi, Loa and Wuchereria bancrofti, Onchocerca volvulus) or made available (Onchocerca volvulus, Brugia malayi larval cDNA library) so that screening with defined patient sera, patient T cells or parasite DNA could be performed. Recombinant antigens and probes have been identified that a) induce T cell responses in an antigen-specific manner, b) may be in part protective in onchocerciasis; c) can distinguish among related filarial species by restriction fragment length polymorphisms, PCR or direct Southern blotting; d) encode immunoreactive and potentially protective molecules of W. bancrofti; e) identify repeated segments of either the W. bancrofti genome or that of Loa; and f) may be of potential diagnostic importance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000512-03
Application #
3809685
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Ghedin, Elodie; Wang, Shiliang; Spiro, David et al. (2007) Draft genome of the filarial nematode parasite Brugia malayi. Science 317:1756-60
Ravi, Varatharajalu; King, Te Piao; Andersen, John F et al. (2005) Strongyloides stercoralis recombinant NIE antigen shares epitope with recombinant Ves v 5 and Pol a 5 allergens of insects. Am J Trop Med Hyg 72:549-53
Kerepesi, Laura A; Keiser, Paul B; Nolan, Thomas J et al. (2005) DNA immunization with Na+-K+ ATPase (Sseat-6) induces protective immunity to larval Strongyloides stercoralis in mice. Infect Immun 73:2298-305
Gomez Gallego, Sara; Loukas, Alex; Slade, Robert W et al. (2005) Identification of an astacin-like metallo-proteinase transcript from the infective larvae of Strongyloides stercoralis. Parasitol Int 54:123-33
Gnanasekar, Munirathinam; Rao, Kakaturu V N; He, Yi-Xun et al. (2004) Novel phage display-based subtractive screening to identify vaccine candidates of Brugia malayi. Infect Immun 72:4707-15
Kerepesi, Laura A; Nolan, Thomas J; Schad, Gerhard A et al. (2004) Human immunoglobulin G mediates protective immunity and identifies protective antigens against larval Strongyloides stercoralis in mice. J Infect Dis 189:1282-90
Mitreva, Makedonka; McCarter, James P; Martin, John et al. (2004) Comparative genomics of gene expression in the parasitic and free-living nematodes Strongyloides stercoralis and Caenorhabditis elegans. Genome Res 14:209-20
Ravi, V; Kubofcik, J; Bandopathyaya, S et al. (2004) Wuchereria bancrofti: cloning and characterization of heat shock protein 70 from the human lymphatic filarial parasite. Exp Parasitol 106:1-10
Wu, Yang; Egerton, Gillian; McCarthy, James et al. (2003) Human immune responses to infective stage larval-specific chitinase of filarial parasite, Onchocerca volvulus, Ov-CHI-1. Filaria J 2:6
Klion, Amy D; Vijaykumar, Aarthi; Oei, Tamara et al. (2003) Serum immunoglobulin G4 antibodies to the recombinant antigen, Ll-SXP-1, are highly specific for Loa loa infection. J Infect Dis 187:128-33

Showing the most recent 10 out of 12 publications