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Title: An evaluation of the Nippostrongylus brasiliensis infection in the rat as a model for the development of subunit vaccines against nematode parasites of ruminants
Author: Ball, Glyn
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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Nippostrongylus brasiliensis is a GI nematode parasite of rodents and is an extensively applied laboratory model for defining the immune mechanisms that mediate worm expulsion. N. brasiliensis infection in the rat shares many similarities with Trichostrongylus infection in ruminants including, importantly, the functional proteins secreted or excreted by the nematode (ES proteins). Several of these ES proteins are potential candidates for vaccines. The aim of this project was to use the rat/Nippostrongylus parasite system as a model for vaccination with recombinant ES proteins. Prior to vaccination trials N. brasiliensis infections of varying levels were investigated and immunological assays were developed to allow the assessment of immune responses to infection and vaccination. Two proteins of interest, a Superoxide dismutase (SOD) and Acetylcholinesterase (AChE), were selected as vaccine candidates. Recombinant AChE was kindly provided for study by Prof Murray Selkirk. A cDNA encoding the SOD was amplified by PCR with a functional enzyme being obtained after expression in E. coli. Vaccination with these two recombinant enzymes was investigated to ascertain their protective capacity and thus their suitability as vaccine candidates. In a preliminary trial with AChE, vaccinated animals showed a 48% reduction in egg output compared to controls, this being associated with changes in antibody and RMCP II levels. The SOD did not induce any protection or a significant immune response. Further trials investigated how the route of administration and adjuvant might affect the protective capacity of these proteins, with protection varying between 0 and 38%. The relevance of these results to future vaccine trials in ruminants is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available