AbstractScabies has afflicted man for hundreds of years and still affects an estimated 300 million people worldwide at any one time. The inability to culture mites in vitro and the lack of natural resources is a major obstacle in the identification and characterisation of scabies-specific antigens. Consequently, the nature of immune responses to scabies infestations remains unclear. Only a handful of treatments remain in use today; most provide only short-term control in endemic areas. The emergence of acaricide resistance to current scabicides suggests the need for alternative treatments in the future.
The work presented in this Thesis describes the construction of the first amplified S. scabiei var. hominis cDNA expression library consisting of approximately 200 000 clones. Immunoscreening experiments using antisera from hyperinfested rabbits led to the identification and characterisation of the first two S. scabiei antigens, Ssag 1 and Ssag 2. Studies performed on these antigens formed the basis of protocols to be executed with other scabies antigens, such as immunisation challenge trials using Prof. Larry Arlian's rabbit model to test for the potential of these antigens as vaccine candidates.
Ssag 1 was shown to be the S. scabiei homologue of the house dust mite allergen M-177, a haemolymph apolipophorin associated with lipid transport. Messenger RNA derived from the above experiments was utilised to construct a λZAP cDNA library to initiate the Scabies Gene Discovery Project. High throughput sequencing of clones generated from this library has identified an abundance of interesting molecules, among which are S. scabiei homologues of major house dust mite allergens.
The success achieved in protecting hosts against a number of ectoparasites by vaccinations with concealed antigens highlights the possibility of a vaccine against scabies. S. scabiei homologues of the various house dust mite gut allergens and other concealed antigens will be targeted during analysis of sequences from the Gene Discovery Project, as potential vaccine candidates. Sequence data generated will be screened to identify other interesting molecules for studies directed at the molecular evolution of the mite, drug resistance and immunotherapy.
|Date of Award||Sep 2001|
|Supervisor||Bart Currie (Supervisor)|