Characterising the B-cell response to Hepatitis C virus infection in patient cohorts: impact on clinical outcomes and implications for vaccine design

Swann, Rachael Elizabeth (2017) Characterising the B-cell response to Hepatitis C virus infection in patient cohorts: impact on clinical outcomes and implications for vaccine design. PhD thesis, University of Glasgow.

Abstract

Hepatitis C virus (HCV) infection is one of the major causes of liver morbidity and mortality worldwide. While effective therapies are now available, if eradication of this virus is to be achieved globally, an effective vaccine is still necessary. During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection or if they could prevent infection or reinfection with the virus.
I investigated the presence and clinical associations of bNAb responses in three cohorts of individuals infected with or exposed to HCV infection. One with chronic HCV infection at differing disease states, one with chronic HCV infection at an early disease state and one group of individuals at high risk of HCV exposure who remained uninfected by conventional testing. I also studied bNAb responses in an individual from a HCV-HIV co-infected cohort who experienced spontaneous clearance of HCV after a post-therapy relapse (‘secondary spontaneous clearance’).
I found a proportion of individuals when exposed to or infected with HCV produce a polyclonal bNAb response which may contribute to viral clearance in some cases. Host genetics and the ability to target multiple neutralising epitopes on the envelope protein are associated with such responses, although resistance mutations to bNAbs do exist in vivo. The presence of bNAbs is associated with lower levels of liver fibrosis. Using next generation sequencing technology in the study of B cell receptors in HCV infection revealed subtle changes in the B cell repertoire on HCV infection, this technology may be used in future to gain insight into the generation of bNAb responses.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Viral hepatitis, liver, cirrhosis, cryoglobulinaemia, B cell repertoire, antibody, envelope proteins, hepatitis C, People who inject drugs, resistance to infection, liver fibrosis progression.
• Subjects: Q Science > QR Microbiology > QR180 Immunology; Q Science > QR Microbiology > QR355 Virology; R Medicine > RZ Other systems of medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Funder's Name: Medical Research Council (MRC), Medical Research Council (MRC), Medical Research Council (MRC)
• Supervisor's Name: Patel, Professor Arvind and McLauchlan, Professor John
• Date of Award: 2017
• Depositing User: Dr Rachael E Swann
• Unique ID: glathesis:2017-8797
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Feb 2018 15:20
• Last Modified: 01 Aug 2022 08:41
• URI: https://theses.gla.ac.uk/id/eprint/8797

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