title: Anti-envelope antibody responses in individuals at high risk of hepatitis C virus who resist infection.
abstract: Injection drug users uninfected by hepatitis C virus (HCV) despite likely repeated exposure through high-risk behaviour are well documented. Factors preventing infection in these individuals are incompletely understood. Here, we looked for anti-HCV-envelope antibody responses in a cohort of repeatedly exposed but uninfected subjects. Forty-two hepatitis C diagnostic antibody- and RNA-negative injection drug users at high risk of exposure were studied and findings compared to healthy controls and cases with chronic HCV infection. Purified IgGs from sera were tested by ELISA for binding to genotype 1a and 3a envelope glycoproteins E1E2 with further testing for IgG and IgM reactivity against soluble E2. Virus-neutralizing activity was assessed using an HCV pseudoparticle system. Uninfected subjects demonstrated significantly greater IgG and IgM reactivities to envelope glycoproteins than healthy controls with IgG from 6 individuals additionally showing significant neutralization. This study is the first to describe humoral immunological responses targeting the HCV envelope, important for viral neutralization, in exposed uninfected individuals. A subset of these cases also had evidence of viral neutralization via anti-envelope antibodies. In addition to confirming viral exposure, the presence of specific anti-envelope antibodies may be a factor that helps these individuals resist HCV infection.
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Swann
authors.affiliation: Hepatology Research Group, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.|South West Liver Unit, Derriford Hospital, Plymouth, UK.
authors.forename: P
authors.initials: P
authors.lastname: Mandalou
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.|School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
authors.forename: M W
authors.identifier: 0000-0002-7871-7103
authors.initials: MW
authors.lastname: Robinson
authors.affiliation: Hepatology Research Group, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.|South West Liver Unit, Derriford Hospital, Plymouth, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Ow
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: S K H
authors.initials: SK
authors.lastname: Foung
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.
authors.forename: J
authors.initials: J
authors.lastname: McLauchlan
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK. Arvind.patel@glasgow.ac.uk.
authors.forename: A H
authors.initials: AH
authors.lastname: Patel
authors.affiliation: Hepatology Research Group, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK. matthew.cramp@nhs.net.|South West Liver Unit, Derriford Hospital, Plymouth, UK. matthew.cramp@nhs.net.
authors.forename: M E
authors.initials: ME
authors.lastname: Cramp
mesh_terms: D000328:Adult; D000917:Antibody Formation; D060467:Disease Resistance; D055030:Drug Users; D004781:Environmental Exposure; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D015819:Substance Abuse, Intravenous; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus
keywords: E1E2; exposed uninfected (EU); injection drug user (IDU); neutralization; neutralizing antibodies