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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:739217 |
| Date | January 2017 |
| Creators | Swann, Rachael Elizabeth |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/8797/ |
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