The study of filarial antigens and their role in human immunity to infection have been hampered by the lack of relevant non-primate models, the difficulty in obtaining parasite material for study, and the antigenic complexity of crude filarial extracts. To circumvent these obstacles, we have screened an Onchocerca volvulus larval cDNA library, a nematode closely related to Loa loa, with serum from """"""""putatively immune"""""""" individuals from a Loa endemic area in Benin, West Africa. These individuals had no clinical or parasitological signs of loiasis nor detectable antifilarial IgG4 antibodies indicating an absence of active infection. However, they supposedly were immune because of an elevated peripheral blood mononuclear cell proliferation to filarial antigens indicating that at some point they were exposed to infective third stage larvae from deerflies. Fusion products from the 57 seropositive clones were tested for their ability to stimulate proliferation of T cells from the same """"""""immune"""""""" individuals, but not from infected individuals or unexposed endemic controls. Based on these results, 5 clones have been selected for further characterization. Because potentially important antigens might be missed using a library from a related species, and because the mechanism of protective immunity in onchocerciasis may differ from that in loiasis, we proceeded with the construction of a L. loa infective third-stage larval (L3) library (titer 106/ml; average insert size 1 kb) from 7,000 L3's collected from Chrysops deerflies. The deerflies were collected in the field and fed on Loa-infected rhesus monkeys. L3 larval antigens with B and T cell epitopes will be identified and characterized as above. Detailed immunologic characterization of the immune responses to these antigens may allow the dissection of protective immune responses from those that cause pathology and provide information essential to the identification of candidate antigens for immunization against filarial infection in humans.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-35
Application #
5219825
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
35
Fiscal Year
1996
Total Cost
Indirect Cost
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Liu, David X; Didier, Peter J; Plauche, Gail et al. (2016) Septicemia in an Indian Rhesus Macaque (Macaca mulatta) associated with Providencia stuartii. J Med Primatol 45:330-332
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