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Title: Detection of type-specific antibody to hepatitis C virus and its application for serological typing
Author: Prescott, Linda Elaine
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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The foundation of this project was the development of an indirect serotyping ELISA for the identification of HCV genotypes 1-3. This thesis is concerned with the further development of the serotyping ELISA. Initially the assay was extended by the incorporation of antigen for recently discovered genotypes 4, 5 and 6. This version of the assay was able to detect type-specific antibody in 87% sera from blood donors and patients with chronic HCV infection from various geographical areas. The specificity of this assay was >97% when compared to genotyping by a PCR method. This serotyping ELISA was applied to a number of different population studies, including the U.S.A., Norway, Pakistan, Egypt and Hong Kong, and in doing so has contributed to current knowledge of genotype distributions worldwide. In an attempt to improve the sensitivity of the assay, peptides corresponding to an additional immunogenic region in NS4 were included and assessed for their contribution to the sensitivity and specificity of the assay. The performance of the serotyping assay was also compared to other PCR-based methods of genotyping. An investigation into samples producing discrepant results in two distinct cohorts was performed by sequence analysis of the 5' NCR, core and NS4 regions. The frequency of discrepant results was higher when testing samples from haemophiliacs than from patients with chronic HCV who had no history of multiple exposure to the virus. Sequence analysis revealed that mis-typing by the ELISA may have resulted from amino acid changes within NS4 from the non-haemophiliac study group, whereas little antigenic variation was identified in discrepant haemophiliac samples. Discrepant results in this multiply-exposed cohort might be explained by the detection of antibody to genotypes from previous or multiple infections. This work has enabled the specific identification of HCV serotypes causing infections worldwide by the development of a highly specific serotyping ELISA. Evidence concerning the possible biological differences between HCV genotypes suggests that serotyping may become an important method in clinical practice for the selection of patients for antivirus treatment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available