Protective immunity in hepatitis C virus infection

Abstract

Primary hepatitis C virus (HCV) HCV infection is associated with viraemia which induces cellular and humoral immune responses in the majority of individuals, regardless of subsequent outcome. HCV-specific immune responses have also been documented in subjects who appear to have never had infection, including in injecting drug users who are at high-risk of infection. These immune responses may be protective, either against incident infection, or against the development of chronic infection. Minute amounts of HCV RNA at levels below detection by conventional assays have been detected in subjects who have cleared HCV infection. This occult virus infection may also occur in high risk injecting drug users, and may therefore provide the antigenic stimulus for the observed immune responses. This study examined the presence of HCV-specific cellular immune responses in a cohort of high-risk, seronegative, aviraemic prisoners using interferon-gamma enzyme linked immunospot assays. Detailed behavioural analyses to identify potential correlates of the presence of these immune responses, and with incident infection were undertaken. In addition, initial efforts to establish an ultra-sensitive, nested reversetranscription polymerase chain reaction to detect both vegetative and replicative HCV RNA strands in highrisk apparently uninfected subjects in this cohort were undertaken. A significant prevalence of HCV-specific cellular immune responses and a high rate of incident infection were found. There was a significant association of measured cellular immune responses with injecting crystal methamphetamine, and surprisingly a negative association between incident infection and tattooing. There was no reduction in the incident infection rate in those with HCV-specific immunity. The studies in this thesis have demonstrated, HCV-specific cellular immune responses in a large cohort of high-risk seronegative subjects. The potential association with occult infection requires further assay development and investigation. The biological significance of the immune responses in protection requires further investigation.