Repertoire and Neutralizing Activity of Antibodies Against Hepatitis C Virus E2 Peptide in Patients With Spontaneous Resolution of Hepatitis C.

Anne Olbrich, Hedda Wardemann, Stephan Böhm, Karen Rother, Che C Colpitts, Florian Wrensch, Thomas F Baumert, Thomas Berg, Julia Benckert

Journal: The Journal of infectious diseases 2020;220(7):1209-1218

PMID: 31165162

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Abstract

Neutralizing antibodies can prevent hepatitis C virus (HCV) infection, one of the leading causes of cirrhosis and liver cancer. Here, we characterized the immunoglobulin repertoire of memory B-cell antibodies against a linear epitope in the central front layer of the HCV envelope (E2; amino acids 483-499) in patients who were infected in a single-source outbreak. A reverse transcription polymerase chain reaction-based immunoglobulin gene cloning and recombinant expression approach was used to express monoclonal antibodies from HCV E2 peptide-binding immunoglobulin G-positive memory B cells. We identified highly mutated antibodies with a neutralizing effect in vitro against different genotype isolates sharing similar gene features. Our data confirm the importance of VH1-69 use for neutralizing activity. The data offer a promising basis for vaccine research and the use of anti-E2 antibodies as a means of passive immunization.

Address: Laboratory for Clinical and Experimental Hepatology, Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany.; Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany.; Max von Pettenkofer Institute, Munich, Germany.; Inserm U1110, University of Strasbourg, France.; Division of Infection and Immunity, University College London, United Kingdom.; Clinic for Hepatology and Gastroenterology, Charité, CVK, Berlin, Germany.

DOI: 10.1093/infdis/jiz274

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MeSH Terms: Adult, Aged, Antibodies, Monoclonal, B-Lymphocytes, Broadly Neutralizing Antibodies, Cohort Studies, Epitopes, B-Lymphocyte, Female, Genotype, HEK293 Cells, Hepacivirus, Hepatitis C Antibodies, Hepatitis C, Chronic, Humans, Immunoglobulin G, Immunologic Memory, Male, Middle Aged, Rho(D) Immune Globulin, Single-Domain Antibodies, Viral Envelope Proteins, Viral Hepatitis Vaccines