Strategies for hepatitis C virus elimination; from point of care testing to investigation of a natural vaccine model

Witkowska, Weronika (2020) Strategies for hepatitis C virus elimination; from point of care testing to investigation of a natural vaccine model. PhD thesis, University of Glasgow.

Abstract

Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis with over 70 million people affected worldwide. Recent advances in direct acting antivirals for HCV treatment have resulted in sustained virological response rates of more than 90%. Thus, the World Health Organisation (WHO) has developed a global strategy for elimination of the virus by 2030. Major barriers to elimination include the lack of a point-of-care (POC) test for immediate linkage to care and the development of a HCV vaccine.

This first part of this thesis covers experiments aimed towards the development of a novel POC test based on loop mediated isothermal amplification (LAMP). The second section of the thesis addresses the novel phenomenon of secondary spontaneous clearance (SSC), studied as a natural vaccine model to decipher the immune responses involved in spontaneous resolution following treatment relapse.

A double-blind study of HCV LAMP was conducted on RNA samples of all major HCV genotypes and viral loads. The sensitivity and specificity of the assay was 90% and 98%, respectively within less than 25 minutes of incubation which fulfils current WHO recommendations. We developed a user-friendly read-out based on a pregnancy-test like lateral flow device. LAMP has minimal equipment and training requirements with previous field studies making it ideal for a future HCV POC test.

The two cases of SSC post-treatment relapse were studied in comparison with four treatment failure (TF) patients. In both SSC cases, low levels of neutralising antibody were detected at the time of diagnosis but on relapse, a robust and sustained response was generated that reduced the infectivity of autologous viral pseudoparticles expressing HCV envelope proteins – a feature not present in any control patients. Furthermore, significant differences in levels of Th-1 cytokines were noted prior to treatment in SSC but not TF. This natural vaccine model (prime on acute infection, boost on relapse) adds weight to the importance of adaptive immune responses in resolving HCV infection

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Hepatitis C virus, World Health Organisation, point-of-care, loop-mediated isothermal amplification, early diagnosis, secondary spontaneous clearance, treatment relapse, vaccine model, immune response.
• Subjects: Q Science > QR Microbiology > QR180 Immunology; Q Science > QR Microbiology > QR355 Virology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Funder's Name: Engineering and Physical Sciences Research Council (EPSRC), Wellcome Trust (WELLCOTR)
• Supervisor's Name: Thomson, Professor Emma and Cooper, Professor Jonathan
• Date of Award: 2020
• Depositing User: Miss Weronika Witkowska
• Unique ID: glathesis:2020-80244
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 03 Mar 2020 14:22
• Last Modified: 23 Mar 2023 09:55
• Thesis DOI: 10.5525/gla.thesis.80244
• URI: https://theses.gla.ac.uk/id/eprint/80244